Self-MHC restriction of TC cells R. Zinkernagel & P. Doherty
Cloning of the TCR b-chain gene by subtractive hybridization By S. M. Hedrick & M. M. Davis
3 important assumptions made by Hedrick and Davis: • The TCR mRNA would be associated with membrane-bound polyribosomes like the mRNAs that encode other integral membrane proteins. (eliminate ~97% mRNAs) • 98% of the genes expressed in lymphocytes are common to B and T cells. TCR should be in the 2% genes expressed specifically in T cells. (DNA subtractive hybridyzation eliminates 98%) • TCR genes should undergo DNA rearrangements like those observed in the Ig genes of B cells.
Organization of mouse TCR gene segments A productive rearrangement of the a chain gene segments deletes Cd
The CDR3 of the TCR has greater diversity than that seen in immunoglobulins
T-Cell Receptor Complex: TCR-CD3 or ζη CD3 is required for membrane expression of T cell receptors
Structures of the CD4 and CD8 coreceptors or aa dimer
Affinity of TCR for peptide-MHC complexes is weak compared with antibody binding T cell-APC interactions are strengthened by cell-adhesion molecules, including CD2, LFA-1, CD28, and CD45R
The ternary complex Of mouse TCR Bound to MHC Class I and peptide CDR3 CDR3
MHC molecule viewed from above not in contact with peptide
Alloreactivity of T cells: in addition to self-MHC plus antigens, T cells also respond to foreign MHC molecules, a reaction that leads to rejection of allogeneic grafts (transplants in the same species) • Alloantigens: epitopes present on molecules that differ among members of the same species because of genetic variation. • T cells recognize a foreign MHC molecules directly. ~1-5% of all T cells are reactive to alloantigen.