immuno 5: anitgen presentation

What is antigen presentation?

T cells only recognize peptide antigens when presented on MHC molecules; peptide sits in MHC binding groove.

Main function of MHC?

Present peptide antigens to T cells.

Key feature of MHC binding?

One MHC can bind MANY different peptides to sample cellular proteins.

Why is it called MHC?Clinical relevance of MHC variation?

dentified in transplant rejection (histocompatibility).

Causes transplant/graft rejection.

Why is MHC diversity important?

Allows immune system to recognize a wide range of antigens.

Why do individuals have different MHC molecules?

Genetic variation (different alleles).

What are MHC genes called in humans?

HLA (human leukocyte antigens).

MHC Class I types?

HLA-A, HLA-B, HLA-C.

MHC Class II types?

HLA-DP, HLA-DQ, HLA-DR.

How diverse are HLA genes?

Thousands of alleles → very unlikely two people match.

What do MHC I vs II present?

MHC I → endogenous (inside cell) antigens ; MHC II → exogenous (outside cell)antigens.

Where is MHC I expressed?

All nucleated cells.

Which T cells recognize MHC I?

CD8+ T cells (cytotoxic T cells). incl naive and CTLs

Function of CD8+ T cells?

Kill infected host cells.

Where does MHC I peptide loading occur?

Rough ER. where MHC class I are being translated and assmebled

What happens if peptide doesn’t fit MHC I after trying on?

modified or sent back to cytoplasm for reprocessing.

Source of MHC I peptides?

Endogenous proteins (host cell proteins+ intracellular pathogens).

What degrades proteins into peptides?

Proteasome.

How do peptides enter the ER?

TAP transporter moves them from floating in cytosol → ER lumen.

What does tapasin do in the lumen?

Bridges TAP (with peptide poking out) and newly synthesized MHC I to help peptide loading.

What is endoplasmic reticulum aminopeptidase ERAP?

ER enzyme that trims peptides to fit MHC I.

What happens id ERAP doesnt work?

Peptide returned to cytoplasm for additional processing

What happens after peptide binds MHC I?

Complex goes through Golgi → cell surface.

MHC I pathway steps (core flow)?

Protein → proteasome → TAP → ER loading via tapasin → ERAP trimming if needed→ surface display.

Do MHC molecules distinguish self vs foreign peptides?

No—both are presented.

Do MHC molecules distinguish self vs foreign peptides?

No—both are presented. Its the CTL’s job to recognize the MHC+peptide complex as self or nonself.

Where is MHC II expressed?

Only APCs (dendritic cells, macrophages, B cells).

What type of antigens does MHC II present?

Exogenous (phagocytosed extracellular proteins). peptides are not generated in cytoplasm

Which T cells recognize MHC II?

CD4+ helper T cells.

Where are MHC II molecules made?

ER.

What blocks MHC II binding site initially?

Invariant chain (prevents binding of self peptides).

Where does MHC II go after ER?

Through Golgi → shuttled to phagolysosome/endosome.

What happens to invariant chain?

Cleaved by cathepsin (proteolytic) → leaves class II-associated invariant chain

peptide CLIP fragment in peptide binding pocket.

What is CLIP?

Fragment that remains in MHC II binding groove.

How is CLIP removed?

HLA-DM exchanges CLIP for antigenic peptide.

Final step of MHC II pathway?

MHC II + peptide goes to surface → activates CD4+ T cells.

MHC II pathway steps (core flow)?

Endocytosis/phagocytosis → digestion → class II synthesized in ER +invariant chain → cathepsin cleaves chain and leaves CLIP → HLA-DM swap for antigenic peptide → surface.

What happens to exogenous antigens in vesicles?

Broken down by low pH, ROS, and enzymes into peptides.

Big picture difference (must know)?

• MHC I = intracellular → CD8 → kill cells

• MHC II = extracellular → CD4 → coordinate immune response