Adaptive immunity 3

Question 1

Define antigen processing

Which antigens are presented by MHC 1 and 2

Answer 1

Enzymatic process of degrading proteins through proteases into antigenic peptides. It requires ATP and movement of endocytic vesicles.

MHC 2- exogenous antigens
MHC 1- endogenous antigens

Question 2

Describe endogenous antigen processing

What is being processed, where, biological molecules involved

Answer 2

• in cytosol presented on MHC1 to CD8+ T cells (cytotoxic, kill infected cells and tumour cells - neoantigen recognition)
• they originate from proteins produced inside the cell including self protein and foreign protein antigens
• the proteosome unfolds tertiary structure of proteins then cleaves proteins into peptides and amino acids
• TAP proteins are transporters that allow processed antigens to be trafficked from cytosol into lumen of ER

Question 3

Describe TAP proteins

Answer 3

TAP 1 and TAP 2 form a heterodimer in membrane of ER

- TAP pump preferentially transports peptides of 8-15 AA long

Question 4

Why is CTL killing important?

Answer 4

• endogenous pathway has evolved to counteract proliferation of viruses/bacteria and parasites intracellularly.
• viruses can interfere with MHC1 expression to escape killing by CTLs
  e. g. HSV protein ICP47 can selectively bind to TAP and inhibit the transfer of peptides into the ER

Question 5

Describe exogenous antigen processing

What is being processed, where, biological molecules involved

Answer 5

• peptides bound to MHC2 are derived from engulfed pathogens
• acidification of endocytic vesicles activates proteases that degrade proteins into fragments
• MHC2 alpha and beta chains associate in the ER. In the golgi network MHC2 is sorted into vesicles and it is these vesicles that deliver MHC2 to specialised compartments for peptide loading.

Question 6

What prevents MHC2 binding endogenous peptides in ER?

Answer 6

• CLIP blocks binding of peptides to MHC2 in vesicles. Once antigen peptide is present, HLA-DM catalyses the release of CLIP
• Invariant chain is degraded and CLIP is exchanged with foreign peptide
• MHC2 loading takes place in endosomes with acidic pH requires for protein degradation

Question 7

How can viruses inhibit MHC2?

Answer 7

• Adenovirus intereferes with class 2 upregulation in APCs.
• HSV envelope protein (glycoprotein B) reduces MHC2 processing and inhibits production on invariant chain (causes self binding)
• HIV intereferes with class 2 processing

Question 8

How can bacteria inhibit MHC2?

Answer 8

• Leishmania and mycobacteria prevent phagosome-lysosome fusion

Question 9

How are T cell antigens kept apart?

Answer 9

Both classes of MHC traverse through the ER to cell surface but load peptides in different cell compartments

Control occurs through accessory proteins

• Class 1 require TAP, Tapasin
• Class 2 require low pH for removal of Li