The processing and presentation of Antigen

Question 1

What does MHC stand for?

Answer 1

Major Histocompatibility Complex

Question 2

What is the human equivalent of MHC?

Answer 2

Human Leukocyte Antigen

Question 3

What is the mouse equivalent of MHC?

Answer 3

H2

Question 4

What do T cells recognise?

Answer 4

The antigen that is processed into peptides and subsequently presented by MHC. T cells can recognise non-protein antigen modifications but they must be part of a peptide

Question 5

How many versions of MHC are there?

Answer 5

2: MHC-I and II. MHC-I is present on all nucleated cells in the body, erythrocytes lose their MHC after nucleus degradation during development. MHC-II is found on professional antigen present cells such as dendritic cells (not FDCs), macrophages and B cells. MHC-II is also on the thymic epithelium and activated human T cells

Question 6

What is MHC-I specialised for?

Answer 6

Altering cytotoxic T cells into intracellular infection clearance.

Question 7

What is MHC-II specialised for?

Answer 7

Activating T helper cells

Question 8

What are the human equivalents of MHC-I?

Answer 8

HLA-A/B/C

Question 9

What are the human equivalents of MHC-II

Answer 9

HLA-DP/DQ/DR

Question 10

What are the mouse equivalent of MHC-I?

Answer 10

H-2K,D,L

Question 11

What are the mouse equivalent of MHC-II?

Answer 11

I-A & I-E

Question 12

What does MHC-III encode?

Answer 12

It does not encode antigen-presenting molecules, but does encode the complement components C2, C4 and factor B, TNF and lymphotoxin.

Question 13

What is the gene order of HLA?

Answer 13

DP-DQ-DR-B-C-A

Question 14

What are the characteristics of HLA genes?

Answer 14

Highly polymorphic; except for MZ twins, and bind antigenic peptides to present them to the TCR. Beta2 microglobin is not polymorphic. There are 6 different MHC-I on every nucleated cell. High MHC diversity enables recognition of pathogens which are constantly evolving; coevolution with pathogens. At each sub-region locus, an individual can either be homozygous or heterozygous, inherited by simple Mendelian inheritance.

Question 15

Are MHC- genes codominantly expressed?

Answer 15

Yes and they are present on the cell surface. Each indibidual can therefore express 12 different MHC molecules if heterozygous at each subregion. Cross pairing of MHC-II molecules = individuals can express more versions of MHC.

Question 16

Describe MHC-I binding

Answer 16

They bind antigenic peptides of 8-9 amino acid residues in size, generated from endogenous antigens by protelolytic degradation in immunoproteasomes (a proteasome modified to cleave proteins into peptides of appropriate length 9-15 amino acids). Peptides are then exported to the lumen of the ER by TAP 1 or TAP 2 transporter channels whe3re they associate with the newly synthesised MHC-I molecule. pMHC is then transferred to the cell surface.

Question 17

Describe MHC-II binding

Answer 17

MHC-II bind long ~15 amino acid peptides derived from exogenous agents taken up by endocytosis/phagocytosis. Proteolytic cleavage occurs in the endosomal compartment.

Question 18

Are the exogenous/ endogenous pathway compartmenalised?

Answer 18

Not entirely and cross presentation can also occur where exogenous antigens can be presented by MHC-I and endogenous antigens by MHC-II.

Question 19

Describe the structure of MHC

Answer 19

MHC-I: beta pleated sheet supports an alpha helix between which there is a cleft where antigenic peptides are located for antigen presentation. 1 large alpha chain with three domains. B2 microglobin is also present, with one transmembrane chain.
MHC-II is similar in structure to MHC-II however two alpha helices are in class II. Two cahins; two domains and both have transmembrane anchor.
A peptide-binding groove is common to class I and II however the groove is longer in II with open ends for binding longer peptides. In I, grooves are closed at ends. Most of the polymorphic amino acid residues of the different MHC alleles are found in the bdingin groove and pockets. Each MHC variant can bind a range of different peptide sequences so long as the peptides share characteristic residues able to interact with the MHC at key anchor positions.

Question 20

How do peptides bind to MHC?

Answer 20

Through non-covalent reactions; electrostatic, hydrogen bond, Van Der Waals and hydrophobic interactions.
Multiple interactions occur between many TCRs on the surface of the T cell and many MHC-peptide complexes on the surface of the MHC-bearing cell. Grooves are located on the beta-pleated sheet.