IMM: BLOCK 2: COMPREHENSIVE OVERVIEW PRACTICE PROBLEMS

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Questions and Answers

What is the primary role of Major Histocompatibility Complex (MHC) molecules in the immune system?

To directly kill infected cells

To serve as a memory for previous infections

To produce antibodies in response to pathogens

To display antigen peptides to T cells (correct)

Which of the following statements about MHC molecules is true?

All types of cells express MHC II molecules

MHC I is expressed by all nucleated cells (correct)

MHC II can be found on resting T cells

MHC molecules are only found in humans

What characteristic of MHC molecules contributes to individual diversity in immune responses?

Their exclusive presence in all humans

The absence of genes from both parents

A uniform structure for all individuals

Multiplicity of their alleles (correct)

What is true regarding peptide binding in MHC I molecules?

MHC I primarily presents endogenous peptides Signup and view all the answers

How does MHC II differ from MHC I in terms of expression?

MHC II is mainly found on professional APCs Signup and view all the answers

What are the major loci for the human MHC class II gene complex?

DP, DQ, DR Signup and view all the answers

What does the term 'amateur antigen presentation' refer to in relation to T cell activation?

Low avidity interaction with inadequate co-stimulation Signup and view all the answers

Which types of peptides do MHC II molecules primarily present?

Exogenous peptides from extracellular sources Signup and view all the answers

What is the role of tapasin in the peptide-loading process of MHC I?

It stabilizes the empty conformation of the peptide-binding groove. Signup and view all the answers

What is the function of ERAP in the MHC I processing pathway?

To modify peptides to fit into MHC I when they are too long at the N-terminal end. Signup and view all the answers

Which chaperone binds to the monoglucosylated N-linked glycan in MHC I?

Calreticulin Signup and view all the answers

How does the interaction between TAP and MHC I occur?

In the endoplasmic reticulum. Signup and view all the answers

What happens to MHC I after it binds to a peptide?

MHC I is exported from the endoplasmic reticulum. Signup and view all the answers

What type of peptides does MHC I primarily bind?

Peptides produced in the cytosol. Signup and view all the answers

What role do the alpha 1 and 2 domains of MHC I play during peptide binding?

They widen the groove to accommodate peptide binding. Signup and view all the answers

What distinguishes MHC I processing from MHC II processing?

MHC I processes peptides exclusively from intracellular sources. Signup and view all the answers

What is the primary role of the peptide binding groove formed by MHC I molecules?

To noncovalently bind an 8-9 amino acid sequence Signup and view all the answers

Which statement best describes MHC I molecules?

They are highly polymorphic with more than 100 alleles at each locus. Signup and view all the answers

What is the significance of MHC restriction in T cell activation?

It ensures T cells can only recognize antigens presented by antigen-presenting cells. Signup and view all the answers

What is the binding preference of CD8+ T cells in relation to MHC molecules?

They bind to the alpha3 domain of MHC I. Signup and view all the answers

What characteristic distinguishes MHC II binding grooves from MHC I binding grooves?

MHC II grooves can accommodate longer peptides, 18-20 amino acids. Signup and view all the answers

What could be an indirect effect of the 'Sweaty T-Shirt' study on human attraction?

Supporting the role of MHC genes in pheromone detection. Signup and view all the answers

Which of the following statements is true regarding nonclassical MHC I molecules?

They have limited variability and may present carbohydrate fragments. Signup and view all the answers

What role does the beta2-microglobulin (beta2m) play in the structure of MHC I molecules?

It stabilizes the closed peptide cleft of MHC I. Signup and view all the answers

Study Notes

MHC Molecules: A Summary

Membrane-bound proteins that display antigen peptides to T cells.
Encoded by genes from both parents, ensuring diversity and a unique MHC pattern for each individual.
Genes are found in all mammals and help the immune system recognize self cells.

MHC I vs MHC II

MHC I: Found on all nucleated cells. Presents peptides from the cytosol, which are usually derived from degraded proteins. Interacts with CD8+ T cells.
- Composed of a heavy chain (alpha) and a light chain (beta2-microglobulin).
- The alpha chain has three domains: alpha1, alpha2 (form the peptide-binding groove), and alpha3 (interacts with beta2m).
- Presents peptides of 8-9 amino acids.
- Has restricted variability and tissue distribution, with limited functions in presenting carbohydrates and peptide fragments.
- Examples: HLA-A, HLA-B, and HLA-C
MHC II: Mainly expressed by professional antigen-presenting cells (APCs). Presents peptides derived from extracellular proteins that have been taken up by endocytosis. Interacts with CD4+ T cells.
- Composed of an alpha and a beta chain.
- Each chain has an amino-terminal domain and an immunoglobulin-like domain.
- Presents peptides of 18-20 amino acids.
- Examples: HLA-DP, HLA-DQ, and HLA-DR

MHC Processing and Presentation

MHC I Processing:
- Begins in the cytosol with the degradation of proteins by proteasomes.
- Peptides are transported from the cytosol to the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP).
- In the ER, peptides bind to MHC I molecules.
- If the peptide is too long, endoplasmic reticulum aminopeptidase (ERAP) trims the peptide into the correct length.
- The peptide-loaded MHC I complex is then transported to the cell surface via exocytic vesicles.
MHC II Processing:
- Extracellular proteins are taken up by endocytosis and transported to lysosomes.
- In lysosomes, proteins are degraded into peptides.
- Peptides associate with MHC II molecules in endocytic vesicles.
- MHC II-peptide complexes are transported to the cell surface.

MHC Restriction

T cell receptors (TCRs) cannot bind free antigens in the body, they require an antigen-presenting cell (APC) with MHC to present the antigen.
CD8+ T cells are restricted to MHC I, while CD4+ T cells are restricted to MHC II.
- CD8 co-receptor binds to the alpha3 domain of MHC I, ensuring MHC I presents peptides only to CD8+ T cells.
- CD4 co-receptor binds to the beta2 domain of MHC II, ensuring peptides bound by MHC II stimulate only CD4+ T cells.

"Sweaty T-Shirt" Study

Study aimed to explore how a man's MHC genes could be detected by women through their sense of smell.
Men wore clean T-shirts for two nights, and women were asked to rate the attractiveness of the scent of the shirts.

Chaperones Involved in MHC I Loading

Chaperones are crucial in stabilizing the structure of MHC I:
- Tapasin and ERp57 form a heterodimer that stabilizes the empty MHC I peptide-binding groove, allowing for high-affinity peptide binding.
- Calreticulin binds to the MHC I heavy chain and indirectly connects the peptide-loading complex with the TAP transporter, bringing empty MHC I closer to peptides transported from the cytosol.

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Description

This quiz explores the structure and function of Major Histocompatibility Complex (MHC) molecules, highlighting the differences between MHC I and MHC II types. Understand how these molecules play a crucial role in immune response and their genetic diversity among individuals. Perfect for students studying immunology and related fields.