Lecture 13

Organized Notes: MHC, TCR Recognition, and Antigen Processing

1. TCR Recognition of MHC/Peptide

• Co-Receptors Required: CD4 (for MHC II) & CD8 (for MHC I)

• Reference: Figure 4.25 (Janeway’s Immunobiology)

2. MHC Class I: Processing & Presentation

• Peptides Presented by Class I Molecules Are Derived from Intracellular Protein Degradation

  • Proteasome degrades proteins

  • MHC locus genes LMP2 (β1i) & LMP7 (β5i) encode immunoproteasome subunits

  • Cytokine-inducible → produces peptides optimal for MHC I binding

  • Reference: Figure 7-13B

• Peptide Transport into the ER by TAP-1 and TAP-2

  • TAP1/2 genes are within the MHC locus

  • Prefer peptides of 8-16 amino acids with hydrophobic/basic C-terminal residues

  • Reference: Figures 7-14B, 7-15

• Role of MHC Class I in Viral Infections

  • Viral infections upregulate TAP1, TAP2, LMP2, LMP7 → enhances antigen presentation

  • Viruses encode MHC I pathway inhibitors (e.g., Herpes Virus ICP47)

3. MHC Class I & II Expression

• MHC Class I: Expressed by all nucleated cells

• MHC Class II: Expressed by specialized antigen-presenting cells (APCs)

  • Reference: Figure 4.27 (Janeway’s Immunobiology)

4. MHC Class II: Processing & Presentation

• MHC II-Expressing Cells (APCs)

  • Dendritic cells, macrophages, and B cells constitutively express MHC II & provide costimulatory signals

  • Thymic epithelial cells play a role in T cell development

• MHC Class II Molecules Bind Peptides of Various Lengths

  • Peptides: 13-18 amino acids (can be longer)

  • "Anchor residues" stabilize binding

  • References: Figures 4.20, 4.21 (Janeway’s Immunobiology)

• Peptide Loading Process for MHC Class II

  • Peptides come from exogenous proteins

5. Cross-Presentation: When MHC I Presents Exogenous Antigens

• Dendritic cells can phagocytose exogenous antigens & present them on MHC I

• Activates CD8+ T cells → Cross-Presentation

6. Diseases That Exploit the MHC Class II Pathway

• Flesh-Eating Disease, Toxic Shock Syndrome

  • Caused by Staphylococcus & Streptococcus

  • Superantigens (SEA, SEB enterotoxins) induce excessive immune activation