Selection of T cell clones with restricted TCR-CDR3 lengths during in vitro and in vivo alloresponses.

ABSTRACT

In a model of heart allograft rejection in adult congeneic rats mismatched for both class I and class II MHC molecules, we analyzed the TCR beta chain repertoire of T cells infiltrating rejected allografts [graft-infiltrating T cells (GITC)]. Although all BV families were used by GITC, oligoclonal expansions reflected by an altered distribution of TCR beta chain CDR3 lengths were detected throughout the rejection process. Interestingly, expansions involving TCR beta chains with common length and BV usage were recurrently found within distinct individuals at late stages of rejection in vivo and after in vitro mixed lymphocyte culture between donor and naive recipient cells. Sequence analysis of the CDR3 regions within recurrent TCR beta chains comprising either BV2 or BV13 gene segments demonstrated a complete sequence identity between BV2-BJ2S3 junctions derived from GITC in all individuals tested and the presence of conserved amino acids at constrained CDR3 positions within GITC BV13+ junctions derived from most individuals. These results suggest the existence of several major alloantigens responsible for expansion of T cell clones bearing a 'public' beta chain rearrangement within rejected allografts. The demonstration that such clones are also expanded during in vitro mixed lymphocyte reactions provides an experimental approach which might allow molecular characterization of the above major alloantigens and their possible in vivo targeting.