DIVERSE USAGE OF HUMAN T-CELL RECEPTOR GENE SEGMENTS IN HLA-DR1 ALLOSPECIFIC T-CELL CLONES

T-cell recognition of alloantigen involves both the MHC molecule and i ts associated peptide ligand. To understand the relationship between t he specificity of alloantigen recognition and the structure of TCR mol ecules, we have investigated TCR gene utilization by sequencing TCR ge nes from a well-defined allospecific T-lymphocyte clones. Alloreactive TLC consisted of a panel of clones primed to recognize DR1-related al loantigens. Our sequencing results revealed rxcensiuely diverse, but n onrandom, usage of TCR AV and BV gene segments and essentially no cons ervation in CDR3 or junctional sequences. Such observations are consis tent with allospecific TCR that interact with MHC molecules on a gener ic level while recognizing specific peptides. They also reduce potenti al enthusiasm for anti-TCR therapy in allograft rejection.