Self-MHC restriction of the T cell receptor

Self-MHC restriction of T C cells R. Zinkernagel & P. Doherty

Cloning of the TCR  -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.

Structure of the  T-cell receptor and surface IgM

Difference in the structures of the  and  receptors

Limited diversity

Organization of mouse TCR gene segments A productive rearrangement of the  chain gene segments deletes C 

TCR variable- region genes rearrange in a manner similar to Ig gene

Junctional diversity

The CDR3 of the TCR has greater diversity than that seen in immunoglobulins

T-Cell Receptor Complex: TCR-CD3 CD3 is required for membrane expression of T cell receptors or ζη

Structures of the CD4 and CD8 coreceptors or  dimer

CD8 binds to class I by contacting MHC class I  2 and  3 domains

CD4 binds to class II through MHC class II  2 and  2 domains

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

Role of coreceptors in TCR binding affinity

The ternary complex Of mouse TCR Bound to MHC Class I and peptide CDR3

MHC molecule viewed from above not in contact with peptide

CDR regions of mouse TCR  and  chains viewed from above

TCRs interact differently with class I and class II moleucles

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.