MHC Class I & II Antigen Presentation

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Questions and Answers

Describe the functional significance of the 19S regulatory particle's location on both ends of the 20S core particle within the proteasome complex.

The 19S regulatory particles, positioned at both ends of the 20S core, serve to recognize, unfold, and feed ubiquitinated proteins into the proteolytic core for degradation; their presence at both ends ensures efficient substrate entry and processing from either direction.

How does the action of interferons on proteasomes affect antigen presentation, and what is the specific advantage of this alteration?

Interferons induce a switch to immunoproteasomes which produce peptides that have better binding affinity to MHC class I molecules, enhancing antigen presentation. This results in increased presentation of viral peptides, leading to a more effective T cell response.

Explain the mechanism by which TAP facilitates antigen presentation via MHC class I molecules, and what would be the consequence if TAP function was completely inhibited?

TAP transports cytosolic peptides into the endoplasmic reticulum, where they can bind to MHC class I molecules. Inhibition of TAP would prevent the loading of MHC class I molecules with cytosolic peptides, severely impairing the presentation of intracellular antigens to CD8+ T cells.

In the absence of infection, what types of peptides are typically presented by MHC class I molecules, and what is the source of these peptides?

In the absence of infection, MHC class I molecules typically present self-peptides derived from normal protein turnover within the cell. These peptides originate from the degradation of cellular proteins by the proteasome. Signup and view all the answers

Describe the route by which extracellular proteins are processed and presented on MHC class II molecules, and how does this differ from the antigen presentation pathway for MHC class I molecules?

Extracellular proteins are taken up by the cell through endocytosis, phagocytosis, or macropinocytosis, and then degraded into peptides within acidified endocytic vesicles. These peptides bind to MHC class II molecules for presentation. This contrasts with MHC class I presentation, which involves peptides from the cytosol transported into the ER by TAP. Signup and view all the answers

Describe the key differences in the processing pathways that lead to antigen presentation via MHC class I and MHC class II molecules. Include the cellular location where peptide loading occurs for each pathway.

MHC class I presents peptides derived from the cytosol, which are generated by the proteasome. These peptides are then transported into the endoplasmic reticulum (ER) for loading onto MHC class I. MHC class II presents peptides derived from extracellular sources that are taken up via endocytosis/phagocytosis. These antigens are processed in lysosomes, where peptide loading occurs. Signup and view all the answers

Explain the role of ubiquitination in the MHC class I antigen presentation pathway and describe how the proteasome contributes to this process.

Ubiquitination marks proteins in the cytosol for degradation. The proteasome then degrades these ubiquitinated proteins into peptides that can be presented on MHC class I molecules. Signup and view all the answers

Why is it important that MHC class I molecules are expressed by virtually all cells in the body? Provide a specific example to illustrate your answer.

MHC class I expression on virtually all cells allows cytotoxic CD8+ T cells to detect and eliminate any cell that is infected with a virus or has become cancerous. For example, if a lung cell becomes infected with a virus, it will present viral peptides on MHC class I, signaling to cytotoxic T cells to destroy the infected cell. Signup and view all the answers

Considering that MHC class II molecules are primarily expressed on antigen-presenting cells (APCs), describe how the specificity of this expression pattern contributes to the adaptive immune response.

Restricting MHC class II expression to APCs ensures that T helper cells are activated only by cells specialized in antigen uptake, processing, and presentation. This prevents inappropriate T cell activation and ensures that the adaptive immune response is initiated in the correct context. Signup and view all the answers

If a patient's cells were unable to properly acidify endosomes and lysosomes, how would this affect antigen presentation via MHC class II molecules, and what would be the downstream consequences for T cell activation?

Impaired acidification of endosomes and lysosomes would inhibit the activity of acidic proteases, resulting in less efficient breakdown of extracellular proteins into peptides. This would reduce the presentation of peptide-MHC class II complexes and potentially impair activation of CD4+ T cells. Signup and view all the answers

Describe the two distinct pathways by which cross-presentation enables dendritic cells (DCs) to load peptides onto MHC class I molecules.

One pathway involves translocation of ingested proteins from the phagolysosome into the cytosol, followed by proteasomal degradation, TAP-mediated peptide transport into the ER, and loading onto MHC-I. The second pathway involves transport of antigens from the phagolysosome into a vesicular loading compartment and loading onto mature MHC class I molecules through peptide exchange. Signup and view all the answers

Explain how the invariant chain (IC) ensures that MHC-II molecules primarily bind peptides derived from endocytosed proteins, rather than self-peptides present within the endoplasmic reticulum (ER).

The invariant chain (IC) binds to the peptide-binding groove of MHC-II molecules in the ER, preventing premature binding of self-peptides. It also directs the MHC-II molecule to endosomal compartments, where the IC is cleaved, allowing MHC-II to bind peptides derived from endocytosed proteins. Signup and view all the answers

Describe the key differences in the origin and processing of peptides presented by MHC class I versus MHC class II molecules.

MHC class I molecules present peptides derived from proteins degraded in the cytosol by the proteasome, which are then transported into the ER. MHC class II molecules present peptides derived from proteins that have been endocytosed and processed in acidic endosomal compartments. Signup and view all the answers

How does the TAP (Transporter Associated with Antigen Processing) protein contribute to the presentation of peptides by MHC class I molecules?

TAP transports peptides generated in the cytosol into the endoplasmic reticulum (ER), where they can bind to MHC class I molecules. Without TAP, MHC class I molecules would not be able to load peptides effectively, preventing proper antigen presentation to CD8+ T cells. Signup and view all the answers

Explain the functional significance of cross-presentation in the context of viral infections that do not directly infect antigen-presenting cells (APCs).

Cross-presentation enables APCs, particularly dendritic cells (DCs), to present viral antigens on MHC class I molecules, even if the APC itself is not infected. This allows for the activation of CD8+ T cells, which are crucial for eliminating virally infected cells, thus initiating an antiviral immune response. Signup and view all the answers

What is the role of proteasomes in the MHC class I antigen presentation pathway, and how does this differ from the antigen processing that leads to MHC class II presentation?

Proteasomes degrade cytosolic proteins into peptides, which are then transported into the ER for loading onto MHC class I molecules. In contrast, MHC class II presentation involves the degradation of endocytosed proteins in acidic endosomal compartments by proteases, not proteasomes. Signup and view all the answers

Considering that both MHC class I and MHC class II molecules are synthesized in the endoplasmic reticulum (ER), describe the mechanisms that ensure they bind peptides from different cellular compartments (cytosol vs. endosomes).

MHC class I molecules bind peptides in the ER that are transported from the cytosol by TAP. MHC class II molecules are associated with the invariant chain (IC) in the ER, which prevents premature peptide binding and directs them to endosomes, where the IC is cleaved and peptides from endocytosed proteins are loaded. Signup and view all the answers

Why is the expression of MHC class II molecules largely confined to antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells?

MHC class II molecules present peptides derived from extracellular proteins taken up by APCs. These peptides are then presented to helper T cells, initiating an adaptive immune response. Confining MHC class II expression to APCs ensures that T cell activation occurs in the context of antigen presentation, preventing inappropriate immune responses against self-antigens. Signup and view all the answers

Describe the role of the invariant chain (CD74) in MHC class II antigen processing and presentation.

The invariant chain binds to MHC class II molecules in the ER, preventing premature binding of endogenous peptides. It is then cleaved into CLIP, which occupies the peptide-binding groove until it is exchanged for an antigenic peptide in acidified vesicles. Thus ensuring the correct peptide loading. Signup and view all the answers

Explain how HLA-DM facilitates the loading of antigenic peptides onto MHC class II molecules in acidified vesicles.

HLA-DM is an MHC-like molecule that resides in acidified vesicles. It binds to MHC class II, catalyzing the release of CLIP and promoting the binding of antigenic peptides with higher affinity. It essentially edits the peptides bound to MHC II to optimize antigen presentation. Signup and view all the answers

What is cross-presentation, and why is it important in the context of viral infections like Herpes virus?

Cross-presentation is when certain APCs, such as dendritic cells, present exogenous antigens on MHC class I molecules. This is crucial for activating cytotoxic T cells against viruses that infect non-APCs, like Herpes virus infecting epithelial cells. This allows for $\text{CD8}^+$ T cell activation, even if the virus doesn't directly infect APCs. Signup and view all the answers

In the scenario of a Herpes virus infection, why is it important that dendritic cells can activate virus-specific cytotoxic T cells even if they are not directly infected by the virus?

If the virus infects non-APCs like epithelial cells, direct MHC class I presentation is limited. Dendritic cells, through cross-presentation, can engulf infected cells or viral antigens and present viral peptides on MHC class I, initiating a cytotoxic T cell response. This is vital for controlling viral spread and eliminating infected cells. Signup and view all the answers

Compare and contrast the pathways of antigen processing and presentation for MHC class I and MHC class II molecules.

MHC class I presents peptides from cytosolic proteins, processed by the proteasome, to cytotoxic T cells. MHC class II presents peptides from extracellular proteins, processed in acidified vesicles, to helper T cells. MHC class I engages $\text{CD8}^+$ T cells, while MHC class II interacts with $\text{CD4}^+$ T cells. Signup and view all the answers

How does the binding affinity between MHC molecules and presented peptides influence the adaptive immune response?

Higher affinity interactions between MHC molecules and peptides typically result in a more stable complex and prolonged signaling to T cells. This can lead to a stronger and more sustained immune response. On the other hand, low affinity interactions may result in weak or transient T cell activation, potentially leading to immune escape by pathogens. Signup and view all the answers

What would be the consequence if CLIP was not effectively removed from the MHC class II molecule during antigen presentation?

If CLIP was not effectively removed, the MHC class II molecule would remain occupied, preventing the binding of antigenic peptides. This would impair the presentation of foreign antigens to helper T cells, leading to a reduced or absent adaptive immune response. The T cells would not be activated, resulting in a compromised immune response. Signup and view all the answers

MHC class I molecules primarily present fragments of proteins derived from the extracellular environment to CD8+ T cells.

False (B) Signup and view all the answers

Antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells exclusively express MHC class II molecules for presenting antigens to T cells.

False (B) Signup and view all the answers

Peptides derived from the vesicular system are transported into the endoplasmic reticulum and directly loaded onto newly synthesized MHC class I molecules.

False (B) Signup and view all the answers

The proteasome, responsible for generating peptides for MHC class I presentation, is a simple single-subunit enzyme located in the cell nucleus.

False (B) Signup and view all the answers

MHC class II molecules present peptide antigens derived from proteins taken up from the outside, such as by phagocytosis.

True (A) Signup and view all the answers

CD4+ T cells recognize antigens presented by MHC class I molecules, leading to the activation of cytotoxic T cell responses.

False (B) Signup and view all the answers

The 20S core of the proteasome, responsible for protein degradation, consists of four inner rings containing structural subunits and lacks proteolytic activity.

False (B) Signup and view all the answers

Two siblings have a 75% chance of sharing at least one HLA haplotype.

True (A) Signup and view all the answers

Allelic variation in MHC molecules primarily affects regions outside the peptide-binding groove.

False (B) Signup and view all the answers

The most variable part of the T-cell receptor interacts exclusively with the MHC molecule, not the peptide.

False (B) Signup and view all the answers

CDR1 and CDR2 loops of the T-cell receptor primarily contact the peptide component of the peptide:MHC complex.

False (B) Signup and view all the answers

T-cell recognition of antigens is not influenced by MHC molecules, as the T-cell receptor interacts directly with the antigen.

False (B) Signup and view all the answers

MHC restriction refers to the ability of T cells to recognize any peptide, regardless of the MHC molecule presenting it.

False (B) Signup and view all the answers

Peter Doherty and Rolf Zinkernagel discovered the phenomenon of somatic hypermutation in T-cells.

False (B) Signup and view all the answers

The CDR3 region of the T-cell receptor is encoded entirely within the V segment gene.

False (B) Signup and view all the answers

T-cell receptors make contact with MHC molecules through the CDR1 and CDR2 regions exclusively of D region genes.

False (B) Signup and view all the answers

MHC class I molecules primarily present peptides derived from proteins degraded in the nucleus.

False (B) Signup and view all the answers

In cross-presentation, dendritic cells (DCs) load peptides derived from endogenous proteins onto MHC class I molecules.

False (B) Signup and view all the answers

The invariant chain (IC) facilitates peptide binding to MHC class II molecules in the endoplasmic reticulum.

False (B) Signup and view all the answers

MHC class II molecules are primarily expressed by all nucleated cells.

False (B) Signup and view all the answers

TAP (Transporter Associated with Antigen Processing) is responsible for transporting peptides into the endosome for MHC-II loading.

False (B) Signup and view all the answers

MHC class I molecules present peptides to CD4+ T cells, leading to their activation.

False (B) Signup and view all the answers

Peptide loading onto MHC class II molecules occurs in acidic endosomal compartments following the cleavage of the invariant chain.

True (A) Signup and view all the answers

Cross-presentation is a mechanism that allows certain dendritic cells to present endogenous antigens on MHC class II molecules.

False (B) Signup and view all the answers

MHC-I molecules that are not loaded with peptides can still travel to the cell surface.

False (B) Signup and view all the answers

Flashcards

α:β T-cells

Recognize antigen-derived peptides presented on MHC molecules.

MHC Class I

Expressed by virtually all cells; presents fragments from the cytosol; recognized by CD8+ T cells.

MHC Class II

Expressed by APCs (DCs, macrophages, B cells); presents fragments from outside the cell; recognized by CD4+ T cells.