07 - T-cell receptor gene diversity.docx

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Department
Immunology
Course
IMM250H1
Professor
Victor Barac
Semester
Fall

Description
T-cell Receptor Gene Diversity T Cell Receptor (TCR) – Ig superfamily mem+er receptor + – Restricted to CD4 (helper) and CD8 (killer) T lymphocytes – Always membrane bound – Antigen binding domain also contains 2 CDRs  CDR3 is the main antigen contact  CDR1 and CDR2 contact MHC receptors on another cell MHC restriction of T cell recognition T Cell receptor diversity – Generated through the same mechanism as Ig diversity  Involves RAG-1, RAG-2, RSS, all the same enzymes & P- and N- nucleotide addition – TCR α and β chain domains ≈ light chain and heavy chain of Ig  TCR α  V – J – C  TCR β  V – D – J – C [ slightly more variable than α] Gene structure and function of TCR – Variable parts are essentially the same as Ig’s  Shape of antigen binding site is more consistent  CDR1 and CDR2 are less variable  CDR3 is more variable  no somatic hypermutation – Functionally, TCRs only work as cell surface proteins (no secretion)  Don’t actually pass the signal that turns on the T cell themselves (they have assistants)   C domain region of gene is simpler  only 1 Cα and 2 very similar Cβ o No known functional difference – Ig stuff where binding gets better as it binds more doesn’t happen with T cells Combinatorial diversity – TCR covers cellular and humoral immunity  Igs just do humoral  T cells need to do more stuff  need  diversity –  diversity in TCR CDR3 domain is b/c of  combinatorial and jxnal diversity α / β vs. γ / δ TCR + + – All CD4 and CD8 T cells have α / β TCR – Small # of T cells have γ / δ TCR  γ / δ TCR is also a heterodimer  Predicted protein structure of each chain is similar to α / β o i.e. constant domain w/ variable on top  No crystal structure  unsure about ligands  lipids? HSPs? Free ligands? – γ / δ TCR also generated by rearrangement  Fewer V segments than Ig
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