Lecture 4: TCRs and BCRs Flashcards
Antigen
Any substance that elicits a T/B cell response
Epitope
The part of the antigen that contacts the antigen receptor
BCR (immunoglobulin) structure
- 2 identical L chains, 2 identical H chains
- Fab (antigen binding) region w/ L+H, CDR1-3
- Fc (constant) region w/ H
- Hinge region joining Fab and Fc
Ig class
Class and effector function defined by Ig Fc region (A, D, E, G, M); Fc region genes align with class (α, δ, ε, γ, μ)
TCR structure
α + β dimers; each dimer has constant + variable regions (CDR1-3 on variable)
- CDR1/2 interface w/ MHC
- CDR3 interfaces w/ peptide
B cell development
- Pluripotent SC
- HSC
- Pro-B
- Large Pre-B (Pre-BCR)
- Small Pre-B (IC μ H chain)
- Immature B (IgM)
- Mature B (IgM, IgD)
T cell development
- SC
- Double negative pro-T cell
- Pre-T cell (Pre-TCR; TCRβ)
- Double positive immature T cell (αβ TCR)
- Lineage commitment
RAG1/RAG2
Proteins specifically required for somatic gene recombination of BCR/TCR
XLA
X-Linked Agammaglobulinemia; deficiency in Bruton’s Tyr kinase (BTK) resulting in no B cells due to block in development
Somatic gene recombination
Process by which gene segments within BCR/TCR genes are randomly brought together during B/T cell maturation
Ig/TCR gene segments
IgH/TCRβ: V, D, J, constant segments
IgL/TCRα: V, J, constant segments
Combinatorial diversity
Diversity obtained from random recombination of VJ/VDJ segments of light/α and heavy/β chains
Junctional diversity
Diversity obtained due to deliberately imperfect joining of junctional genes between V, D, J on CDR3. Achieved with P nucleotide insertions and N region additions via Terminal deoxynucleotidyl-Transferase (TdT)
CDRs
Complementarity Determining Regions; hypervariable regions on antigen binding domains from 1 to 3 (CDR3 is most diverse)
B cell selection
B cell selection is less intense; only negative selection as part of central tolerance
T cell selection
- Positive selection of double positive T cells (req. weak interaction w/ MHC; no binding -> death by neglect)
- Negative selection (strong binding -> apoptosis)
