Lectures 9-11: MHC, Antigen Presentation, TCR

Question 1

The peptide binding region of the MHC I molecule consists of which domains

Answer 1

α₁ and α₂ domains

Question 2

The heavy chain of the MHC molecule is also called the

Answer 2

α chain (as it is composed of three α domains)

Question 3

The Ig-like region of the MHC I molecule is composed of which domains

Answer 3

ß₂ microglobulin and α₃

Question 4

The Ig-like region of the MHC II molecule is composed of which domains

Answer 4

α₂ and β₂

Question 5

The peptide binding region of the MHC II molecule is composed of which domains?

Answer 5

α₁ and β₁

Question 6

The CD4 molecule binds to which domain of the MHC class II?

Answer 6

β2 domain

Question 7

MHC Class I molecules are expressed on which cells?

Answer 7

All nucleated cells, but not all to the same degree.

e.g. neuronal tissue tends to have low levels of class I MHC

Question 8

MHC class II molecules are expressed on which cells?

Answer 8

On professional antigen-presenting cells (APC)

e.g. macrophages, Langerhan’s cells, dendritic cells, B cells

Question 9

Invariant chain (Ii)

Answer 9

Binds peptide binding groove in ER

Targets class II to endosomal compartment

Cells from Ii knockout mice express greatly reduced levels of class II on their cell surface

Question 10

HLA-DM/H-2M

Answer 10

Dimeric class II like molecule

Colocalises with Class II and Ii in MIIC compartment

Important for peptide loading

Mice/Cells lacking HLA-DM have severely impaired Ag presentation capacity

Class II molecules predominantly occupied by CLIP (CLass II associated Invariant chain Peptide).

Question 11

TAP

Answer 11

Heterodimeric protein (TAP1/TAP2)

Related to the multidrug resistance pumps - ABC (ATP binding cassette) family of transport proteins

Binds ATP

Transports peptides from the cytosol into the endoplasmic reticulum (optimal length 8-16 amino acids)

Preference for C-terminal hydrophobic residues

Encoded by genes encoded within the MHC region

Expression is upregulated by γinterferon

Question 12

The proteasome

Answer 12

Large multi-subunit protease complex present in the cytoplasm

Highly conserved

Lmp2, Lmp7, MECL1 and PA28 are “alternate” proteasome components that appear to have a role in Ag-processing.

• Not normally expressed in most cells
• Expression is induced by γIFN
• Replace other components of the proteasome in the complex
• Preferentially generate peptides 8-16 amino acids in length with basic or hydrophobic C-terminal residues
• Enhanced TAP transport and MHC binding (hydrophobic C-terminal anchor residues are common)
• Mice deficient in Lmp2/7 express MHC class I molecules but have an impaired T cell response to certain viruses.

Question 13

TCR contains how many Ig-like domains

Answer 13

Four

Question 14

The β chain of the TCR resembles the __ chain of an Ig

Answer 14

heavy chain

Question 15

True or false:

TCR genes do not undergo somatic hypermutation.

Answer 15

True

Question 16

Superantigens

Answer 16

Select TCR just on Vβ sequence compared with MHC-bound peptides which select TCR based on complete CDR sequence pattern of αβ-chain