TCR and MHC

Question 1

What encodes TCR polypeptides?

Answer 1

Rearranging gene segments (V, D, J) during T cell development in the thymus.

Question 2

What mechanisms are involved in TCR gene rearrangement?

Answer 2

Similar to Ig gene rearrangement.
Uses recombination signal sequences (RSS) and enzymes (RAG-1/2).

Question 3

How does TCR diversity arise?

Answer 3

1. Multiple V, D and J gene segments
2. Combinatorial diversity between V, D and J segments
3. Junctional diversity during gene joining

Question 4

What is a key difference between TCR and BCR?

Answer 4

TCR is never secreted.
No somatic hypermutation (SHM) occurs in TCR genes.

Question 5

Where are MHC molecule genes located in humans?

Answer 5

Chromosome 6 (HLA complex).

Question 6

How are MHC molecules expressed?

Answer 6

Co-dominantly.

Question 7

Which cells express MHC class I molecules?

Answer 7

All nucleated cells.

Question 8

Which cells express MHC class II molecules?

Answer 8

Antigen-presenting cells (APCs), e.g., B cells, macrophages, dendritic cells.

Question 9

How can MHC class II expression be induced?

Answer 9

By interferons during inflammation.

Question 10

Why are MHC genes highly polymorphic?

Answer 10

Allows binding of a vast range of peptides.
Provides an evolutionary advantage by enabling responses to diverse pathogens.

Question 11

What are the downsides of high MHC polymorphism?

Answer 11

1. Increased risk of immune-mediated diseases (e.g., autoimmune diseases).
2. Reduced pool of available donor organs for transplantation.

Question 12

How many different MHC molecules can an individual express?

Answer 12

Class I: Up to 6 molecules (HLA-A, HLA-B, HLA-C; heterozygous at each locus).
Class II: Up to 6 molecules (HLA-DP, HLA-DQ, HLA-DR; heterozygous at each locus).

Question 13

What types of antigens are presented by MHC molecules?

Answer 13

MHC class I: Endogenous antigens (e.g., viral proteins).
MHC class II: Exogenous antigens (e.g., bacterial proteins).

Question 14

How are endogenous antigens processed for MHC class I?

Answer 14

1. Synthesised in cytoplasm
2. Cleaved into peptides by proteasome
3. Transported to ER by TAP transporter
4. Loaded onto MHC class I
5. MHC-I/peptide complex transported to cell surface

Question 15

What proteins are involved in the MHC class I pathway?

Answer 15

Proteasome
TAP transporter
Tapasin and calreticulin (peptide-loading complex)

Question 16

How are exogenous antigens process for MHC class II?

Answer 16

1. Endocytosed into vesicles
2. Cleaved by acid proteases in vesicles
3. Vesicles fuse with MHC class II-containing vesicles
4. Peptides loaded onto MHC class II
5. MHC-II/peptide complex transported to cell surface

Question 17

What prevents premature binding of peptides to MHC class II in the ER?

Answer 17

Binding of the invariant chain to the groove

Question 18

How are peptides loaded onto MHC class II?

Answer 18

Invariant chain is degraded in the endocytic pathway, leaving CLIP in the groove.
HLA-DM facilitates displacement of CLIP and loading of antigen-derived peptides.

Question 19

What is unique about BCR and TCR diversity?

Answer 19

Diversity within an individual.
Genes formed by rearranged segments joined imprecisely.
Clonally distributed (each B/T cell has a unique BCR/TCR)

Question 20

What is unique about MHC class I and II diversity?

Answer 20

Diversity at the population level.
Limited number of forms in an individual.
Polymorphic residues affect peptide-binding, enabling presentation of diverse peptides.

Question 21

Which cells are specialised APCs?

Answer 21

Macrophages
Dendritic Cells
B cells

Question 22

How do APCs activate T cells?

Answer 22

Present extracellular antigens on MHC class II to helper CD4+ T cells

Question 23

What is the role of non-APC cells in antigen presentation?

Answer 23

Express MHC class I and present intracellular antigens to cytotoxic CD8+ T cells

Question 24

What accessory molecules are involved in the MHC class I pathway?

Answer 24

TAP and LMP

Question 25

What accessory molecules are involved in the MHC class II pathway?

Answer 25

HLA-DM