IMM: BLOCK 2: COMPREHENSIVE OVERVIEW PRACTICE PROBLEMS

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.

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.