MHC

Question 1

Purpose of MHC

Answer 1

• Display Ag to T cells
• Epitope binds to MHC molecule
• Used interchangeably with HLA in humans

Note: MHC is not specific for particular antigen (but T cell is)

Question 2

Where is MHC 1 found + function

Answer 2

• Found on all nucleated cells (not on RBC)
• Display waste products
• Alert T killer cells when something isn’t right INSIDE cell
• Clear endogenous antigens (tumour cells, pathogen, virus infected cells)

Recognised by CD8 T cells

Question 3

Where is MHC 2 found + function

Answer 3

• Found only on APC (DC, macrophages, B cells)
• Inform T helper cells that problems exist OUTSIDE of cells
• Clear exogenous antigens (toxins)

Recognised by CD4 T cells

Question 4

Structure of MHC 1

Answer 4

Ag peptide ends buried in MHC (shorter peptide)

Ag binding site cleft by alpha 1 and alpha 2 chains.

2 non-identical chains.

Question 5

Structure of MHC 2

Answer 5

Ag peptide ends pop out like sausage in hot dog (longer peptide)

Ag binding site cleft by alpha and beta chains

2 nearly identical chains

Question 6

What kind of peptides do MHC-1 present

Answer 6

Peptides from cytosol

Transported in ER by TAP1/2 transporters, placed into MHC 1 molecules, then transported to cell surface

Question 7

What kind of peptides do MHC-2 present

Answer 7

Peptides from degraded proteins in vesicles

Some pathogens (e.g. TB) replicate in endosomes, which become more acidic as it progresses towards cell interior -> protein degraded in vesicle

Question 8

Describe cross presentation on MHC-1

Answer 8

Some DCs form peptide:MHC-1 complexes from peptides that weren’t generated within their own cytosol

Peptides from extracellular sources presented on MHC-1 molecules

Question 9

Which HLA molecules are MHC 1 molecules

Answer 9

HLA-A, HLA-B, HLA-C

Question 10

Which HLA molecules are MHC 2 molecules

Answer 10

Dr, Dq, Dp, Dm, Doa, Dob are MHC 2 molecules (HLA-D genes)

Question 11

What 2 properties of MHC help them to avoid pathogen evasion

Answer 11

Polygenic: many different genes code for MHC

and

Polymorphic: many variants of each gene e.g. HLA-A1 - HLA-A303). Variations mainly occur in peptide binding groove

Question 12

What and whose MHC molecule is targeted by immune response when the donor and recipient differ at MHC

Answer 12

Immune response directed against non-self MHC 1 molecules

Question 13

Describe MHC restriction

Answer 13

TCR recognises the combination of MHC: antigen.

So TCR activated by influenza virus peptide:HLA-A1, will not recognise the same influenza virus peptide:HLA-A2