Human leukocyte Antigen (HLA)

Question 1

Where are the genes of the MHC located?

Answer 1

Chromosome 6 in humans (Chromo. 17 in mice)

Question 2

What is the function of MHC molecules? (4)

Answer 2

• generate IR to specific Ag
• Determines the cells to be targeted by T cells
• Required for presenting Ag to TCR on T lymphocytes
• distinguishes self from non-self => rejection of non-self

Question 3

What different forms of antigen do B and T cells recognize?

Answer 3

B: Soluble Ag: protein, nucleic acid, poly saccharides, lipids, some chemicals
T: Not soluble Ag: fragments of protein

Question 4

What size peptides do MHC class I and class II molecules bind?

Answer 4

MHC 1: 8-9 AA peptides

MHC 2: 12-17 AA peptides

Question 5

Which domains of MHC class I molecules most polymorphic and which are most conserved?*

Answer 5

Polymorphic: alpha 1 & 2 (distant from cell surface)
Conserved: alpha 3 & beta 2-M*

Question 6

Which domains of MHC class II molecules most polymorphic and which are most conserved?

Answer 6

Polymorphic: alpha 1 & beta 2 (distant from cell)
Conserved: alpha 2 & beta 2 (near cell membrane)

Question 7

To what T cell types do MHC class I and class II present peptides and what specific T cell molecule is expressed for each type?

Answer 7

MHC I: CD8 CTL

MHC II: CD4 Th

Question 8

What cell types are MHC class II molecules expressed?

Answer 8

professional expressed on APC

Question 9

How are MHC molecules able to bind a large variety of different peptides?

Answer 9

• Binding site of MHC molecule is flexible (@ intracell. stage)
• binding site can fold around peptide

Question 10

Describe how eXogenous antigens are processed. (8 steps)

Answer 10

1. Pro. APC phagocytose Ag => phagosome
2. phatosome + lysosome => phagolysosome
3. Ag broken down by acid & enzymes
4. MHC II is formed in rER w/ CD74 (on the binding groove)
5. CD74 degrades => clip fragment (DM)
6. MHC II fuse w/ …lysosome
7. HLA-DM exchanges DM w/ Ag fragment
8. MHC II mvoes to surface for presentation

Question 11

Describe how eNDogenous antigens are processed. (7)

Answer 11

1. pathogens - infected cell in cytoplasm
2. proteasome cleaves proteins -> 15 AA peptides
3. cytosolic enzymes cleave further => 8-15 AA
4. peptide transport to ER by TAP-1 & TAP-2
5. MHC I is synthesised w/ B2-M
6. TAP transfers peptide onto MHC I
7. MHC I / peptide complex moves via Golgi app. to surface of cell

Question 12

Why are there no T cell responses to self proteins when most of the MHC molecules on the surface of cells are bound to self proteins?

Answer 12

• bc T cell activation requires a second signal - not produced by self-proteins
• called co-latopr factor OR second signal

Question 13

the T cell restriction in MHC 1 & MHC 2?

Answer 13

• CD8 CTL = MHC 1 restricted

- CD4 Th = MHC 2 restricted

Question 14

3 classes of genes within MHC & which cell/s biund to & which cells recognise them

Answer 14

• MHC 1: on nucleated cells recognised by CD8 receptor on CTL recognise
• MHC 2: on APC recognised by CD4 Th cells
• MHC 3