Podcast
Questions and Answers
How do the peptide-binding characteristics of MHC class I molecules differ from those of MHC class II molecules?
How do the peptide-binding characteristics of MHC class I molecules differ from those of MHC class II molecules?
- MHC class I molecules have peptide-binding clefts that are closed at both ends. (correct)
- MHC class I molecules present peptides with anchor residues distributed along the length of the peptide.
- MHC class I molecules generally bind larger peptides than MHC class II molecules.
- MHC class I molecules have peptide-binding clefts that are open at both ends.
What is the predominant role of the TAP complex in antigen processing?
What is the predominant role of the TAP complex in antigen processing?
- It facilitates the transport of peptides from the endoplasmic reticulum to the cytosol.
- It transports peptides from the cytosol into the endoplasmic reticulum for MHC class I loading. (correct)
- It prevents MHC class II molecules from binding to peptides in the endoplasmic reticulum.
- It loads peptides onto MHC class II molecules within endocytic vesicles.
Which of the following best describes the function of the invariant chain (Ii) in MHC class II antigen presentation?
Which of the following best describes the function of the invariant chain (Ii) in MHC class II antigen presentation?
- It promotes the loading of antigenic peptides onto MHC class I molecules in the ER.
- It stabilizes the interaction between the T-cell receptor and the MHC class II molecule.
- It facilitates the assembly of MHC class I molecules with $\beta_2$-microglobulin.
- It prevents MHC class II molecules from binding peptides in the endoplasmic reticulum and directs MHC class II molecules to endocytic compartments. (correct)
How does the binding of a superantigen to MHC class II molecules and T-cell receptors differ from that of a conventional peptide antigen?
How does the binding of a superantigen to MHC class II molecules and T-cell receptors differ from that of a conventional peptide antigen?
What is the significance of the polygenic nature of MHC genes in the context of immune responses?
What is the significance of the polygenic nature of MHC genes in the context of immune responses?
Which cellular process is directly inhibited by the presence of the CLIP (Class II-associated Invariant chain Peptide) molecule?
Which cellular process is directly inhibited by the presence of the CLIP (Class II-associated Invariant chain Peptide) molecule?
Which of the following statements accurately compares the structure of MHC class I and MHC class II molecules?
Which of the following statements accurately compares the structure of MHC class I and MHC class II molecules?
What is the primary consequence of a genetic defect that impairs the function of the TAP transporter?
What is the primary consequence of a genetic defect that impairs the function of the TAP transporter?
Which cellular compartment is the primary site for the loading of peptide antigens onto MHC class II molecules?
Which cellular compartment is the primary site for the loading of peptide antigens onto MHC class II molecules?
What is the role of calreticulin and tapasin in MHC class I antigen presentation?
What is the role of calreticulin and tapasin in MHC class I antigen presentation?
The diversity of T-cell receptors (TCRs) is generated through somatic recombination of gene segments. Which of the following gene segments are rearranged to form the variable region of the TCR $\beta$ chain?
The diversity of T-cell receptors (TCRs) is generated through somatic recombination of gene segments. Which of the following gene segments are rearranged to form the variable region of the TCR $\beta$ chain?
In T-cell development, what is the significance of positive selection?
In T-cell development, what is the significance of positive selection?
Which of the following statements best describes the role of CD3 molecules in T-cell activation?
Which of the following statements best describes the role of CD3 molecules in T-cell activation?
What is the function of the immunological synapse formed between a T cell and an antigen-presenting cell (APC)?
What is the function of the immunological synapse formed between a T cell and an antigen-presenting cell (APC)?
Which of the following is an immediate early event in T-cell activation following T-cell receptor engagement?
Which of the following is an immediate early event in T-cell activation following T-cell receptor engagement?
How does the mechanism of action differ between CTLA-4 and CD28 in regulating T-cell activation?
How does the mechanism of action differ between CTLA-4 and CD28 in regulating T-cell activation?
What is the outcome of T-cell anergy when a T cell recognizes its cognate antigen on an APC that lacks co-stimulatory molecules?
What is the outcome of T-cell anergy when a T cell recognizes its cognate antigen on an APC that lacks co-stimulatory molecules?
Superantigens can activate a large proportion of T cells, leading to excessive cytokine production. What region of the T-cell receptor do superantigens bind to?
Superantigens can activate a large proportion of T cells, leading to excessive cytokine production. What region of the T-cell receptor do superantigens bind to?
Which of the following is a key function of IL-2 (Interleukin-2) in T-cell activation?
Which of the following is a key function of IL-2 (Interleukin-2) in T-cell activation?
What is the primary function of negative selection during T-cell development in the thymus?
What is the primary function of negative selection during T-cell development in the thymus?
What is the role of the co-stimulatory molecule B7 in T-cell activation?
What is the role of the co-stimulatory molecule B7 in T-cell activation?
In the context of T-cell activation, what is the function of ZAP-70?
In the context of T-cell activation, what is the function of ZAP-70?
How does the process of positive selection in T-cell development ensures self-MHC restriction?
How does the process of positive selection in T-cell development ensures self-MHC restriction?
What is the role of Lck kinase in T-cell receptor signaling?
What is the role of Lck kinase in T-cell receptor signaling?
What describes the distribution and function of adhesion molecules, such as LFA-1 and ICAM-1, in T-cell activation?
What describes the distribution and function of adhesion molecules, such as LFA-1 and ICAM-1, in T-cell activation?
Which of the following is the primary mechanism by which T cells undergo apoptosis?
Which of the following is the primary mechanism by which T cells undergo apoptosis?
How are the genetic rearrangements that contribute to T-cell receptor diversity mediated?
How are the genetic rearrangements that contribute to T-cell receptor diversity mediated?
What would be the most likely outcome if a genetic mutation disabled the expression of MHC class II molecules?
What would be the most likely outcome if a genetic mutation disabled the expression of MHC class II molecules?
Which of the following best explains how a dendritic cell initiates T-cell activation?
Which of the following best explains how a dendritic cell initiates T-cell activation?
What is the significance of the ITAMs (immunoreceptor tyrosine-based activation motifs) in T-cell activation?
What is the significance of the ITAMs (immunoreceptor tyrosine-based activation motifs) in T-cell activation?
How does a fixed antigen-presenting cell (APC) – one lacking co-stimulatory molecules – influence T-cell activation?
How does a fixed antigen-presenting cell (APC) – one lacking co-stimulatory molecules – influence T-cell activation?
Given its role in T-cell activation, what direct effect would a drug that inhibits the interaction between CD28 and B7 have?
Given its role in T-cell activation, what direct effect would a drug that inhibits the interaction between CD28 and B7 have?
Which process is directly associated with the release of cytochrome c from the mitochondria during T cell apoptosis?
Which process is directly associated with the release of cytochrome c from the mitochondria during T cell apoptosis?
What is the primary significance of the observation that T cells in G0 state before activation?
What is the primary significance of the observation that T cells in G0 state before activation?
Which of the following surface interactions is required for T cell activation?
Which of the following surface interactions is required for T cell activation?
How does negative selection impact T-cell development and overall immune function?
How does negative selection impact T-cell development and overall immune function?
Which component of the T-cell receptor complex is directly responsible for transducing the activation signal into the cell?
Which component of the T-cell receptor complex is directly responsible for transducing the activation signal into the cell?
Which of the following outcomes can happen to a T-cell presented with antigen in the absence of sufficient co-stimulation?
Which of the following outcomes can happen to a T-cell presented with antigen in the absence of sufficient co-stimulation?
Flashcards
Major Histocompatibility Complex (MHC)
Major Histocompatibility Complex (MHC)
A complex of genes encoding MHC class I and II molecules, and proteins involved in antigen processing.
MHC class I function
MHC class I function
Present peptides derived from intracellular pathogens to T cells.
MHC class II function
MHC class II function
Present peptides derived from extracellular pathogens to T cells.
β2-microglobulin
β2-microglobulin
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Peptide-binding cleft
Peptide-binding cleft
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Class I MHC characteristics
Class I MHC characteristics
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Class II MHC characteristics
Class II MHC characteristics
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Antigen processing
Antigen processing
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Cytosolic pathway
Cytosolic pathway
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Endocytic pathway
Endocytic pathway
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Transporter Associated with Antigen Processing (TAP)
Transporter Associated with Antigen Processing (TAP)
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Invariant chain (Ii)
Invariant chain (Ii)
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HLA-DM
HLA-DM
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T-cell Receptor (TCR)
T-cell Receptor (TCR)
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αβ T cells
αβ T cells
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Combinatorial Diversity
Combinatorial Diversity
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N-region addition
N-region addition
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CD4 and CD8
CD4 and CD8
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CD4+ T cells
CD4+ T cells
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CD8+ T cells
CD8+ T cells
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Class I MHC knockout
Class I MHC knockout
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T cell maturation
T cell maturation
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Engagement Signal
Engagement Signal
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T-Cell Activation Genes
T-Cell Activation Genes
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Anergic genes
Anergic genes
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Costimulatory Activity
Costimulatory Activity
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No proliferation
No proliferation
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Superantigens
Superantigens
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Memory T-cell
Memory T-cell
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Apoptosis
Apoptosis
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Study Notes
- Kuby Immunology, Sixth Edition, Chapter 8 is about the Major Histocompatibility Complex and Antigen Presentation
- The copyright for this edition is 2007 by W. H. Freeman and Company
Mouse H-2 Complex
- Encoded on chromosome 17 in mice.
- Includes Class I, Class II, and Class III genes.
- Class I region contains the K and D regions.
- Class II region contains the IA and IE regions.
- Class III region contains the S region, encoding complement proteins and TNF-α/TNF-β.
- Not all haplotypes express H-2L.
Human HLA Complex
- MHC genes are encoded on chromosome 6 in humans.
- Includes Class I, Class II, and Class III genes.
- Class I region contains the B, C, and A regions.
- Class II region contains the DP, DQ, and DR regions.
- Class III region contains the C4, C2, and BF regions.
- All regions have various gene products, such as HLA-A, HLA-B, etc.
Class I MHC Molecule
- Has 3 membrane-distal domains: α1, α2, and α3.
- The α1 and α2 domains form the peptide-binding cleft.
- It has 1 membrane-proximal domain: α3 (Ig-fold structure).
- β2-microglobulin associates with Class I molecules.
- Includes a transmembrane segment and a cytoplasmic tail.
Class II MHC Molecule
- Has 2 membrane-distal domains: α1 and β1.
- Has 2 membrane-proximal domains: α2, β2.
- Α1 and β1 domains form the peptide-binding cleft.
- Includes a transmembrane segment and a cytoplasmic tail.
- B2/α2 have structural similarity to FC
Class I and Class II DNA & mRNA
- Class 1 Molecules are made from various components
- Includes Leader (L), α1, α2, α3, transmembrane(Tm) and cytoplasmic domains (C C)
- Components of molecule are used together for assembly
- Class II Molecules have similar structure and order of assembly as Class 1
Peptide Binding by Class I and Class II
- Class 1 molecules are closed on both ends, and Class II molecules are open at both ends
- Common peptide motifs involved in binding
- Class 1 bind 8-10 amino acids with hydrophobic carboxyl-terminal anchor
- Class 2 bind 13-18 amino acids with residues distributed along the length of the peptide
MHC Proteins
- MHC proteins are polygenetic
- Cells can have 1,000-4,000 proteins each
- Can have up to 100,000 proteins per cell
Antigen Processing
- Antigen must be degraded into peptides for presentation
- APCs present antigen
- Fixation is a necessary part of the process
Cytosolic Pathway
- Endogenous antigens are processed.
- This pathway involves the proteasome and TAP (Transporter Associated with Antigen Processing).
- Ubiquitin mediates this process
- Peptide-class 1 MHC complex happens here
Endocytic Pathway
- Exogenous antigens are broken down in endocytic compartments
- The peptides binds to class II MHC
- Peptides are created in peptide-class II MHC complex
Tapasin
- Tapasin is a TAP-associated protein
- It forms the molecular complex that prevents MHC I from binding
- Calreticulin, and ERp57 also involved
- B2-microglobulin is also key
Endocytic Pathway
- Invariant chains prevent MHC II from binding peptides
- HLA-DM causes exchanged of CLIP for antigenic peptide
- The endosome containing antigen can be accessed at a low PH of 4.5-6
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