Chapter 9 T-cell Receptor Dr. Capers

Kuby IMMUNOLOGY Sixth Edition Chapter 9 T-Cell Receptor Copyright © 2007 by W. H. Freeman and Company Kindt Goldsby Osborne

T cell receptor vs B cell receptor  T cell receptor is only membrane bound ○ Doesn’t appear in soluble form like antibodies so more difficult to assess it’s structure  Antigen binding of T cell receptor is weaker than that of antibodies  Antigen recognized by T cells is not antigen alone but antigen associated with MHC molecules

 (a) T cell receptor (TCR) is specific for peptide A  (b) Right MHC haplotype but wrong antigen (peptide B)  (c) Right antigen (peptide A) but wrong haplotype

 T cell receptor (TCRs) ○ TCR heterodimers are similar to immunoglobulins Therefore they are classified in immunoglobulin superfamily Resembles Fab fragment

 TCRs ○ Associate with MHC – αβ TCR ○ Do not associate with MHC – γδ TCR - Much remains to be learned of function of γδ TCR

Rearrangement of TCR genes  Similar to that of Ig Rearrangement of α and γ chains ○ V, J, and C segments Rearrangement of β and δ chains ○ V, D, J, and C segments

 Generation of TCR diversity (a lot like Ig) ○ Multiple germ-line gene segments ○ Combinatorial V-(D)-J joining ○ Junctional flexibility ○ P-region nucleotide addition ○ N-region nucleotide addition ○ Combinatorial association of light and heavy chains  However, there is no somatic mutation with TCR ○ May be to ensure that after thymic selection, the TCR doesn’t change to cause self-reactive T cell

TCR-CD3 Complex  Accessory molecules help in signal transduction after interaction of T cell with antigen 2 Zeta ζζ chains Heterodimer of delta epsilon γε chains Heterodimer of delta epsilon εδ chains

T cell accessory molecules  T cells can be divided into 2 populations: ○ CD4+ Recognize antigen associated with Class II MHC OR ○ CD8+ Recognize antigen associated with Class I MHC ○ CD4 and CD8 function as coreceptors and assist with signal transduction

 Affinity of TCR for peptide-MHC complexes is enhanced by coreceptors

 Allogenic – genetically different individuals of same species  Alloreactivity of T cells is puzzling: ○ Evidence supports that T cells can only respond to antigen+MHC ○ However, T cells can recognize a foreign MHC molecule alone -As with transplants