Immunobiology Chapter 4: B-cell and T-cell receptors
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Questions and Answers

Explain how the avidity effect enhances the functional binding strength of an antibody with two antigen-binding sites, compared to a hypothetical antibody with only one binding site. Provide a scenario where this avidity effect would be particularly crucial for effective immune response.

Avidity refers to the increased overall binding strength due to multiple interactions. An antibody with two binding sites can bind more strongly because even if one bond breaks, the other can maintain the interaction. This is crucial when antigens are sparse or when the individual binding affinity is low, ensuring stable and effective binding.

Compare and contrast the mechanisms by which B cells and T cells recognize antigens, highlighting the structural adaptations that allow each cell type to fulfill its specific role in the adaptive immune response.

B cells use antibodies to directly bind to native antigens in their original conformation, while T cells use T cell receptors (TCRs) to recognize processed peptide fragments presented by MHC molecules. This difference reflects B cells' role in neutralizing extracellular pathogens and T cells' role in targeting intracellular infections.

Describe the structural components of a typical antibody molecule and explain how these components contribute to its ability to both recognize and eliminate pathogens.

An antibody consists of two heavy chains and two light chains, with variable regions at the tips forming antigen-binding sites. The constant regions mediate effector functions, such as complement activation or binding to Fc receptors on immune cells, facilitating pathogen elimination.

How does the recognition of antigens by T cell receptors (TCRs) differ fundamentally from that of B cell receptors, and why is this difference crucial for the adaptive immune response?

<p>TCRs recognize peptide fragments of antigens presented by MHC molecules on other cells, whereas BCRs (antibodies) recognize native antigens directly. This difference is crucial because it allows T cells to detect intracellular pathogens by scanning peptides displayed on cell surfaces, enabling the elimination of infected cells.</p> Signup and view all the answers

Explain how secreted antibodies contribute to the humoral immune response, and provide two specific examples of how antibody binding to a pathogen can lead to its inactivation or elimination.

<p>Secreted antibodies bind specifically to foreign antigens, marking them for destruction or neutralizing them. Examples include: (1) neutralization of a virus by blocking its ability to enter host cells and (2) opsonization, where antibodies coat bacteria to enhance phagocytosis by macrophages.</p> Signup and view all the answers

Explain how the structural differences between MHC class I and MHC class II molecules influence the length and binding of peptides presented to T cells.

<p>MHC class I binds shorter peptides (8-10 amino acids) due to the peptide being bound at both ends within the cleft. MHC class II binds longer peptides (13-17 amino acids) with overhangs, as the peptide is bound by several residues within the cleft rather than at the ends.</p> Signup and view all the answers

Describe the roles of the $\alpha$ and $\beta$ chains in the structure and function of MHC class II molecules, including their membrane spanning properties and contribution to the peptide-binding cleft.

<p>Both the $\alpha$ and $\beta$ chains of MHC class II span the membrane. The $\alpha1$ and $\beta1$ domains together form the peptide-binding cleft, while the $\alpha2$ and $\beta2$ domains have an immunoglobulin fold.</p> Signup and view all the answers

How does the non-covalent binding of peptides to MHC molecules contribute to the stability and function of the MHC-peptide complex?

<p>Non-covalent binding of peptides to MHC molecules stabilizes the MHC molecule itself. The stable MHC-peptide complex is crucial for effective presentation to T cells, triggering an immune response only when a peptide is bound.</p> Signup and view all the answers

Explain the significance of knowing the peptide-binding preferences of different MHC alleles in the context of tumor immunology and the development of tumor vaccines.

<p>Understanding MHC allele-specific peptide-binding preferences allows for the design of tumor vaccines that present tumor-associated antigens effectively to T cells, enhancing the immune response against cancer cells. Algorithms can be applied to predict binding.</p> Signup and view all the answers

Compare and contrast the overall structure of MHC Class I and MHC Class II molecules, focusing on the number of transmembrane proteins, the domains that form the peptide binding groove, and the typical length of peptides that each presents.

<p>MHC Class I has one transmembrane protein ($\alpha$ chain) and presents 8-10 amino acid peptides, with the peptide binding groove formed by the $\alpha1$ and $\alpha2$ domains. MHC Class II has two transmembrane proteins ($\alpha$ and $\beta$ chains) and presents 13-17 amino acid peptides, with the peptide binding groove formed by the $\alpha1$ and $\beta1$ domains.</p> Signup and view all the answers

Explain how the structural features of the immunoglobulin domain, particularly the beta sheets and disulfide bonds, contribute to the overall stability and function of antibody molecules.

<p>The anti-parallel beta sheets stabilized by internal disulfide bonds form a beta sandwich, providing a stable and characteristic 'immunoglobulin fold.' This fold is crucial for antigen recognition and binding.</p> Signup and view all the answers

Illustrate with an example, how the flexibility of the hinge region in an antibody molecule influences its ability to bind multiple antigens, differentiating between affinity and avidity in this context.

<p>The hinge region's flexibility allows antibodies to bind to antigens at varying distances and angles. While affinity refers to the strength of a single binding site, avidity considers the overall strength of multiple binding sites which is enhanced by hinge flexibility allowing better overall binding.</p> Signup and view all the answers

Describe how the cleavage of an antibody by pepsin or papain results in functionally distinct fragments (Fab and Fc), and outline the specific roles these fragments play in immune responses.

<p>Papain cleavage yields two Fab fragments, which bind antigens, and one Fc fragment. Pepsin cleavage yields F(ab')2 that can bind antigen and pFc'. Fab fragments mediate antigen recognition, while the Fc fragment interacts with immune cells and complement to trigger effector functions.</p> Signup and view all the answers

Compare and contrast the structural and functional differences among the five major immunoglobulin isotypes (IgM, IgD, IgG, IgA, IgE), focusing on their distribution, effector functions, and roles in different types of immune responses.

<p>IgM is the first antibody produced in response to an antigen and is effective at complement activation. IgD's function is less defined, but it plays a role in B cell activation. IgG is the most abundant isotype in serum and provides long-term immunity. IgA is found in mucosal secretions and protects against pathogens at mucosal surfaces. IgE is involved in allergic reactions and parasitic infections.</p> Signup and view all the answers

Explain how the hypervariable regions (CDRs) contribute to the diversity of antigen binding and how their specific arrangement and sequence variations enable antibodies to recognize a vast array of different antigens.

<p>The hypervariable regions, or CDRs, form the antigen-binding site and are highly variable in amino acid sequence. This variability allows for the creation of diverse binding sites capable of recognizing a wide range of antigens with high specificity. There are 6 total CDRs, 3 on the light chain and 3 on the heavy chain.</p> Signup and view all the answers

Describe the main characteristics of antibody structure including the molecular weight, number and type of chains, what type of bonds hold it all together, and what part of the antibody binds antigen.

<p>IgG has a molecular weight of 150 kDa, comprised of two 50 kDa heavy chains and two 25 kDa light chains linked by disulfide bonds. The antigen binding site is composed of the variable heavy and variable light chain domains.</p> Signup and view all the answers

The hypervariable regions are also known as complementarity-determining regions. Explain why they have this name and how that impacts their function.

<p>They are named CDRs because the surface they form is complementary to that of the antigen they bind. This allows for tight binding of the antigen so its presence can be detected by the immune system.</p> Signup and view all the answers

Explain how Complementarity Determining Regions (CDRs) contribute to the specificity of antibody-antigen interactions. What would happen if the amino acid sequence of the CDRs were changed?

<p>CDRs form the antigen-binding site and their specific amino acid sequences determine the shape and charge distribution that allows the antibody to bind a specific antigen. Changing the amino acid sequence would alter the binding site, thus changing or eliminating the antibody's affinity for its target antigen.</p> Signup and view all the answers

Describe the structural similarities between a T cell receptor (TCR) and a Fab fragment of an antibody. How do these similarities contribute to their function?

<p>Both TCRs and Fab fragments exhibit an Ig-like domain folding pattern with two anti-parallel β sheets. Their variable domains can be superimposed, and both contain CDR loops. These structural similarities allow both molecules to recognize and bind to specific target antigens, albeit in different contexts.</p> Signup and view all the answers

Explain how the presentation of antigens by MHC class I and MHC class II molecules differs, including the source of the antigens and the types of T cells that recognize them.

<p>MHC class I molecules present fragments of proteins from the cytosol of virtually all cells and are recognized by cytotoxic CD8+ T cells. MHC class II molecules, expressed by antigen-presenting cells (APCs), present fragments of proteins taken up from the outside and are recognized by CD4+ T cells.</p> Signup and view all the answers

A patient has a mutation that impairs the folding of the constant domains of their T cell receptors (TCRs). How might this mutation affect the TCR's function and the patient's immune response?

<p>Impaired folding of the constant domains can affect the stability and interactions of the TCR with other proteins, such as CD3, which are essential for signal transduction. This can lead to reduced or absent T cell activation, impairing the patient's ability to mount an effective immune response.</p> Signup and view all the answers

Explain the significance of the estimated number of different TCR clones in a human (2 x 10^7). How does this diversity contribute to the adaptive immune response?

<p>The high number of different TCR clones illustrates the vast repertoire of T cells capable of recognizing a diverse array of antigens. This diversity ensures that the immune system can respond to virtually any foreign peptide presented by MHC molecules, providing broad protection against pathogens.</p> Signup and view all the answers

If an APC is presenting an antigen via MHC class II, describe the origin of that antigen and the type of T cell the APC will interact with. How does this interaction initiate an immune response?

<p>The antigen presented via MHC class II originates from proteins taken up from the outside of the APC. The APC will interact with CD4+ T cells. This interaction initiates an immune response by activating the CD4+ T cell, which can then differentiate into helper T cells that assist in activating other immune cells like B cells and cytotoxic T cells.</p> Signup and view all the answers

Describe how the structure of the antigen-binding site of an antibody is related to its function. What specific regions of the antibody are most crucial for this interaction, and why?

<p>The antigen-binding site of an antibody is shaped by the complementarity-determining regions (CDRs), which are loops located at the variable domains. The amino acid composition and structure of the CDRs determine the specificity and affinity of the antibody for its target antigen. These regions are crucial because they directly interact with the antigen.</p> Signup and view all the answers

Explain the role of MHC molecules in T cell activation. What would happen if an individual had a genetic defect that prevented the expression of MHC class I molecules?

<p>MHC molecules present processed antigens to T cells, allowing T cell receptors (TCRs) to recognize and bind to the antigen-MHC complex, which is necessary for T cell activation. Without MHC class I expression, CD8+ T cells cannot be properly activated, leading to a compromised immune response against intracellular pathogens and tumor cells.</p> Signup and view all the answers

Compare and contrast the roles of CD4+ and CD8+ T cells in the adaptive immune response. How do their interactions with MHC molecules dictate their specific functions?

<p>CD4+ T cells, interacting with MHC class II, primarily function as helper cells, coordinating immune responses by activating other immune cells, such as B cells and macrophages. CD8+ T cells, interacting with MHC class I, are cytotoxic cells that directly kill infected or cancerous cells. Their interactions with MHC molecules determine their respective roles in orchestrating and executing immune responses.</p> Signup and view all the answers

An experimental drug is designed to disrupt the interaction between the TCR and its co-receptor (either CD4 or CD8). Predict the effect of this drug on T cell activation and the subsequent immune response, considering the roles of both CD4+ and CD8+ T cells.

<p>Disrupting the interaction between the TCR and its co-receptor would significantly impair T cell activation. For CD4+ T cells, this would reduce their ability to activate B cells and other immune cells, diminishing the antibody response and overall coordination of the immune response. For CD8+ T cells, it would weaken their cytotoxic activity against infected cells. The overall effect would be a weakened and less effective adaptive immune response.</p> Signup and view all the answers

The antigen-binding site of an antibody is primarily determined by the constant regions, which dictate the overall structure and effector functions.

<p>False (B)</p> Signup and view all the answers

T cell receptors (TCRs) are composed of alpha and beta chains, each possessing variable domains that differ between T cell clones, allowing for diverse antigen recognition.

<p>True (A)</p> Signup and view all the answers

Each T cell expresses approximately 300,000 different TCRs on its surface to maximize antigen recognition breadth.

<p>False (B)</p> Signup and view all the answers

The T cell receptor (TCR) possesses a chain structure that mirrors that of a complete antibody molecule, including both Fab and Fc regions.

<p>False (B)</p> Signup and view all the answers

TCR variable domains contain five CDR loops, which contribute to the specificity of antigen recognition.

<p>False (B)</p> Signup and view all the answers

A T cell receptor (TCR) recognizes antigens presented by MHC molecules, specifically binding to the MHC molecule alone, independent of the peptide.

<p>False (B)</p> Signup and view all the answers

MHC class I molecules present fragments of proteins taken up from the external environment, enabling the immune system to respond to extracellular pathogens.

<p>False (B)</p> Signup and view all the answers

MHC class II molecules are exclusively expressed by all nucleated cells in the body to facilitate broad immune surveillance.

<p>False (B)</p> Signup and view all the answers

CD4+ T cells, which interact with MHC class II molecules, typically function as cytotoxic T cells, directly killing infected cells.

<p>False (B)</p> Signup and view all the answers

T cell receptors (TCRs) exclusively interact with the peptide component of the peptide:MHC complex, disregarding any interaction with the MHC molecule itself.

<p>False (B)</p> Signup and view all the answers

The complementarity-determining regions (CDRs) of the T cell receptor (TCR) are not involved in the interaction with the peptide:MHC complex.

<p>False (B)</p> Signup and view all the answers

T cell receptors (TCRs) exhibit affinity for MHC molecules regardless of the presence of a bound peptide.

<p>True (A)</p> Signup and view all the answers

CD8, a monomeric protein, interacts with MHC class II molecules to stabilize T cell interactions.

<p>False (B)</p> Signup and view all the answers

The interaction of CD4 and CD8 with MHC molecules occurs at variable sites, specific to the presented peptide.

<p>False (B)</p> Signup and view all the answers

CD4 and CD8 act as co-receptors by decreasing the T cell's sensitivity to antigens by approximately 10-fold.

<p>False (B)</p> Signup and view all the answers

MHC class II molecules are exclusively expressed on all nucleated cells in the body.

<p>False (B)</p> Signup and view all the answers

MHC class I molecules are expressed on all nucleated cells and are crucial for detecting viral infections; they are also highly expressed on all leukocytes apart from APCs.

<p>False (B)</p> Signup and view all the answers

T cell receptors (TCRs) recognize chemically diverse antigens directly, similar to how immunoglobulins function.

<p>False (B)</p> Signup and view all the answers

In MHC class I molecules, both the alpha and beta-2 microglobulin chains span the cell membrane.

<p>False (B)</p> Signup and view all the answers

The peptide-binding cleft in MHC class II molecules is formed by the folding of the α1 and β3 domains.

<p>False (B)</p> Signup and view all the answers

MHC molecules covalently bind to antigenic peptides to ensure stable presentation to T cells.

<p>False (B)</p> Signup and view all the answers

Bound peptides destabilize MHC molecules, leading to their rapid degradation if not bound to an antigen.

<p>False (B)</p> Signup and view all the answers

MHC class I molecules typically bind peptides that are 13-17 amino acids in length.

<p>False (B)</p> Signup and view all the answers

Peptides bind to MHC class II molecules exclusively through interactions at their termini, ensuring uniform binding orientation.

<p>False (B)</p> Signup and view all the answers

Flashcards

Lymphocyte Activation

Lymphocytes activated during infection/vaccination eliminate pathogens.

T-cell Function

Recognize & kill infected cells, activate other leukocytes.

B-cell function

Activated by T cells to secrete antibodies.

Antibody Function

Bind to foreign structures (antigens) to inactivate them.

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Antigen Recognition

Binds directly, T Cell Receptor requires MHC presentation.

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MHC Class I Structure

Has two polypeptide chains: an alpha chain and beta2-microglobulin. Only the alpha chain spans the membrane. Alpha1 and alpha2 form the peptide-binding cleft with a beta-sheet floor and alpha-helical walls.

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MHC Class II Structure

Has two polypeptide chains: an alpha chain and beta chain. Both span the membrane. Alpha1 and beta1 form the peptide-binding cleft, with alpha2 and beta2 having an immunoglobulin fold.

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MHC-Peptide Binding

Peptides bind stably (non-covalently) to MHC molecules. Binding stabilizes the MHC molecule itself.

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MHC Class I Peptide Length

MHC Class I molecules bind short peptides, typically 8-10 amino acids long, via both ends.

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MHC Class II Peptide Length

MHC Class II binds longer peptides (13-17 amino acids) with variable length and anchor residues at various distances from the end.

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Antibody (IgG) Structure

A protein (IgG) with a molecular weight of 150 kDa composed of 2 heavy chains (50 kDa each) and 2 light chains (25 kDa each), linked by disulfide bonds.

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Major Immunoglobulin Isotypes

IgM, IgD, IgG, IgA, and IgE. They differ in their distribution and effector functions within the body.

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Immunoglobulin Domain Folding

Each domain consists of two anti-parallel beta sheets, stabilized by an internal disulfide bond, forming a beta sandwich structure (Immunoglobulin fold).

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Antibody Cleavage Fragments

Pepsin or papain cleavage of antibodies in the hinge region yields Fc (fragment crystallizable) and Fab (fragment antigen-binding) fragments.

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Hinge Region Function

The hinge region allows flexibility in antibody binding of multiple antigens which affects affinity and avidity

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Antigen Binding Site

Antigen binding occurs via hypervariable regions within the variable domains of heavy and light chains.

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Hypervariable Regions (CDRs)

Hypervariable regions, also called complementarity-determining regions (CDRs), are loops that form a surface complementary to the antigen, with 3 CDRs in both heavy and light chains.

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CDRs

Region of antibody that makes contact with the antigen. Shapes the antigen-binding site.

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T Cell Receptor (TCR)

A receptor on T cells that recognizes antigens. It is composed of an alpha and beta chain.

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Va and Vb Domains

Variable regions which differ between different T cell clones and contain CDR loops.

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Antigen Recognition by TCR

TCRs recognize a complex of a foreign peptide bound to an MHC molecule.

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MHC Class I

Expressed by virtually all cells; presents fragments of proteins expressed by the cell itself; interacts with CD8+ T cells.

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MHC Class II

Expressed by antigen-presenting cells; presents fragments of proteins taken up from outside the cell; interacts with CD4+ T cells.

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Antigen-Presenting Cells (APCs)

Cells include dendritic cells, macrophages, and B cells. They express MHC class II.

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CD8+ T Cells

Interact with MHC class I. Recognize antigens presented by MHC I.

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CD4+ T Cells

Interact with MHC class II. Recognize antigens presented by MHC II

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Fab fragment

The T cell receptor resembles this antibody fragment.

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MHC Class II Peptide Binding

Peptides bind to MHC class II via multiple residues within the binding cleft itself.

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MHC Binding Relevance

Knowing MHC peptide-binding preferences helps in tumor vaccine design and de-immunization of therapeutic proteins.

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Complementarity-Determining Regions (CDRs)

Region of antibody that dictates antigen specificity. Formed by hypervariable loops.

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TCR Chains

Two chains, alpha and beta, make up this receptor.

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Va and Vb Domains (TCR)

Variable domains of the TCR, differ between T cell clones.

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Antigen Presentation

Peptide fragments bound to MHC molecules.

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MHC Class I Function

Displays peptides from inside the cell, interacts with CD8+ T cells.

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MHC Class II Function

Expressed on APCs; presents peptides from outside the cell; interacts with CD4+ T cells.

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CD8+ T Cells Function

Recognize antigens presented by MHC I.

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TCR Binding

The T cell receptor (TCR) binds to a peptide:MHC complex, recognizing both the peptide and the MHC molecule.

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TCR CDR Loops

TCR interactions mainly involve the CDR loops of the TCR.

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Peptide-Independent Affinity

TCRs display a baseline affinity for MHC molecules independent of the peptide presented.

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CD4/CD8 Co-receptors

CD4 and CD8 bind to invariant sites on MHC molecules, increasing T cell sensitivity.

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Lck Recruitment

CD4 and CD8 enhance TCR signaling by recruiting Lck to the TCR complex.

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Immune Synapse

CD4 and CD8 stabilize the TCR-MHC complex, aiding in the formation of the immune synapse.

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MHCII Expression

MHCII is highly expressed on professional antigen-presenting cells (APCs): dendritic cells, B-cells, and macrophages.

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MHCI Expression

MHCI is expressed on all nucleated cells, enabling detection of viral infections.

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CD4/CD8 Restriction

T cell binding to MHCI or MHCII is supported by the co-receptors CD8 and CD4, respectively.

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Study Notes

  • The lecture covers antigen recognition by B-cell receptors and T-cell receptors, based on Chapter 4 of Janeway's Immunobiology.
  • The topics include the structure of a typical antibody molecule, the interaction of the antibody molecule with specific antigens, and antigen recognition by T cells.

Lymphocyte Activation and Pathogen Elimination

  • Lymphocytes are activated during infection or vaccination, which helps eliminate pathogens efficiently.
  • Lymphocytes contribute to the specific and efficient elimination of pathogens.
  • T-cells recognize and destroy infected cells and activate other leukocytes.
  • B-cells are activated by pathogen-specific T cells and then secrete antibodies.
  • Antibodies bind specifically to foreign structures (antigens) and make them inactive.

Antibody vs. T Cell Receptor

  • Antibodies directly bind to the native antigen in blood or tissue.
  • T cell receptors (TCRs) only recognize peptide fragments of the antigen when presented on major histocompatibility (MHC) molecules.

Antibodies

  • Antibodies are effector molecules primarily used to fight pathogens in the humoral immune response in the extracellular space.
  • They are present on B cells as a surface receptor for antigens, also known as the B cell receptor (BCR).
  • Antibodies are composed of constant and variable immunoglobulin domains.
  • The variable domains bind the antigen (Ag), and one antibody (Ab) has two Ag binding sites, resulting in an avidity effect.
  • IgG has a molecular weight of 150 kDa, including 2 heavy chains (50 kDa each) and 2 light chains (25 kDa each), linked by disulfide bonds.
  • The antigen-binding site is composed of variable heavy and variable light chain domains.
  • There are 5 major immunoglobulin classes (isotypes): IgM, IgD, IgG, IgA, and IgE.
  • Isotypes differ in their distribution in the body and the effect they trigger ("effector functions").
  • Each domain consists of two anti-parallel β sheets, These are stablisied by an internal disulphide bond. This forms a β sandwich (immunoglobulin fold).
  • Cleavage occurs in the hinge region.
  • The Fc fragment is "fragment crystallizable”.
  • The Fab fragment is "fragment antigen-binding”.
  • The hinge region provides flexibility in antibody (Ab) binding multiple antigens.
  • Antigen binding occurs via the hypervariable regions present in the variable domains of the heavy and light chains.
  • Hypervariable regions are also called complementarity-determining regions (CDRs).
  • CDRs' surface is complementary to the antigen they bind.
  • Each heavy and light chains have 3 CDRs.
  • In total, there are 6 CDRs.
  • These may contact the antigen.
  • The antigen-binding site is shaped by the CDRs (complementarity-determining regions).
  • Noncovalent forces include electrostatic forces, hydrogen bonds, Van der Waals forces, hydrophobic forces, and cation-pi interactions.

T Cell Antigen Recognition

  • The T cell receptor resembles a membrane-bound Fab fragment and is composed of an α and β chain.
  • Variable domains (Vα and Vβ) differ between different T cell clones.
  • Each T cell bears approximately 30,000 identical TCRs on its surface, while the estimated number of different TCR clones in a human is 2 x 10^7.
  • The framework variable domains (Vα and Vβ) can be superimposed with antibody variable domains.
  • Similar to antibodies, each TCR variable domain contains 3 CDR (complementarity-determining region) loops.
  • A T cell receptor (TCR) recognizes antigens in the form of a complex of a foreign peptide bound to an MHC molecule.

MHC Classes

  • MHC class I is expressed by virtually all cells in the body.
  • It presents fragments of proteins expressed by the cell itself (derived from the cytosol).
  • MHC class I is recognized by cytotoxic CD8+ T cells.
  • MHC class II is expressed by antigen-presenting cells (APCs: DCs, macrophages, B cells).
  • It presents fragments of proteins taken up into the APC from the outside and interacts with CD4+ T cells.
  • MHC class I has two polypeptide chains (α chain and β2-microglobulin).
  • Only the α chain spans the membrane.
  • Folded α1 and α2 form a peptide-binding cleft/groove, comprised of a β-sheet floor and two α-helices as "walls".
  • MHC class II has two polypeptide chains (α and β).
  • Both chains span the membrane.
  • Folded α1 and β1 chains form the peptide-binding cleft/groove, comprised of a β-sheet floor and two α-helices as “walls" and α2/β2, having an immunoglobulin fold.
  • MHC molecules bind peptides non-covalently within the cleft, and the bound peptide stabilizes the MHC molecule.
  • MHC class I molecules bind short peptides (8-10 amino acids) through both ends.
  • MHC class II binds longer peptides (13-17 amino acids) by several residues within the groove, which results in overhangs.
  • Knowing the peptide-binding preferences of MHC molecules is relevant for tumor immunology (tumor vaccines) and immunogenicity of therapeutic proteins (de-immunization).
  • The T cell receptor (TCR) binds to the peptide:MHC complex through interactions of its CDR loops that involve both the peptide and the MHC molecule.
  • TCRs display baseline affinity for MHC molecules, which is peptide-independent.
  • T cell contact with MHC molecules involves CD4 and CD8.
  • CD8 is a disulfide-linked heterodimer that binds to MHCI, while CD4 is a monomer (4 Ig-like domains) that binds to MHCII.
  • CD4 and CD8 bind to invariant sites of the MHC molecules.
  • This binding contributes to the overall effectiveness of the T cell response, increasing T cell sensitivity for Ag by approximately 100-fold.
  • CD4 and CD8 are therefore called co-receptors.
  • The roles of CD4 and CD8 are enhancement of TCR signaling via recruitment of Lck to the TCR complex.
  • They also stabilize the interactions between the TCR and MHC complex, forming the immune synapse.
  • MHC I molecules are predominantly expressed on all nucleated cells.
  • This is important for detecting viral infections in these cells.
  • MHC II is highly expressed on professional antigen-presenting cells (APCs) like dendritic cells, B-cells, and macrophages.
  • MHC II is highly expressed on thymic epithelial cells.

Key Takeaways

  • B and T cells use structurally related molecules (TCRs and immunoglobulins) to recognize antigens.
  • TCRs and immunoglobulins are highly variable, with the variability concentrated in the antigen-binding portion.
  • Immunoglobulins can bind a variety of chemically different antigens.
  • αβTCRs only recognize processed antigens (peptides from intracellularly degraded proteins) bound to MHC for cell surface presentation.
  • Two classes of MHC molecules exist with different expression patterns among cells.
  • T cell binding to MHCI or MHCII is supported by the co-receptors CD8 and CD4, respectively.

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Antigen Recognition by B-Cell & T-cell Receptors PDF

Description

Lecture on antigen recognition by B-cell receptors and T-cell receptors, based on Chapter 4 of Janeway's Immunobiology. Topics include antibody structure and interaction with antigens, and antigen recognition by T cells. Lymphocytes are activated during infection, leading to pathogen elimination.

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