Antigen receptors and MHC

Question 1

B cell receptors

Answer 1

Surface membrane-bound forms of IgM
One heavy, one light chain
Variable (antigen binding) and non-variable (constant) regions
Same specificity as when secreted as antibody

Question 2

BCR diversity

Answer 2

Recombination of gene segments
Ig light chain genes have variable, joining and constant segment
Ig heavy chain genes have V, Diversity, J and C segments

Question 3

V(D)J recombination

Answer 3

Regions normally separated by many kilobases of DNA
Formation of loop
RAG2 binds Recombination Signal Sequences (RSSs). RAG1 cleaves DNA
Hairpins opened with exonucleases and Joined with additional N and P nucleotides

Question 4

RAG1/2 deficiency

Answer 4

Severe Combined Immuno-Deficiency (SCID)

Babies born with non-functional RAG1/2 have no circulating B or T cells

Question 5

Allelic exclusion

Answer 5

B cells have two copies of each chromosome

If productive gene rearrangement occurs in one allele, the expression of the other is silenced

Question 6

IgM and IgD expression

Answer 6

Immature B cell has membrane bound IgM.
Mature B cell also has membrane bound IgD with same antigen specificity but different heavy chain constant region.
Caused by alternative splicing (same V joined to different C)

Question 7

BCR signalling

Answer 7

BCR does not signal directly

Associated with Igalpha and Igbeta

Question 8

Secreted IgM

Answer 8

Produced via alternative splicing
Has hydrophobic segment
Functional diversity through class switching from IgM to other class
Diversity also through somatic hypermutation and affinity maturation

Question 9

T cell receptors

Answer 9

Cannot bind antigen alone. Antigen presented by MHC (MHC restriction)

Expression controlled by allelic exclusion

Only one kind of constant region

Question 10

TCR coreceptors

Answer 10

CD3 contains ITAMs that transmit signal to the cell
CD4/8 increase avidity of peptide binding by TCR
CD28 engages CD80/86 on APC for full activation of naive T cell

Question 11

MHC

Answer 11

Major histocompatibility complex
MHCI can be found on all nucleated cells
MHCII expression restricted to APCs

Question 12

Endogenous pathway

Answer 12

Antigens degraded into peptides by proteasomes in the cytosol and assemble with MHCI in the RER

Presented on the surface of APCs to CD8+ CTL cells (cytotoxic)

Question 13

Exogenous pathway

Answer 13

Antigens internalised and degraded with acidic endocytic compartments

Combine with MHCII and presented to CD4+ Th cells

Question 14

Cross presentation

Answer 14

Exogenous antigens access class I presentation pathways. 
Activates CTLs against exogenous antigens and intracellular microbes