Chapter 9

T-cell Receptor

Dr. Capers

Kuby IMMUNOLOGYSixth Edition

Chapter 9T-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

immunoglobulinsTherefore they are classified in immunoglobulin

superfamilyResembles 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 antigen2 Zeta ζζ chainsHeterodimer of delta

epsilon γε chainsHeterodimer 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