P. Douillard et al., SELECTION OF T-CELL CLONES WITH RESTRICTED TCR-CDR3 LENGTHS DURING IN-VITRO AND IN-VIVO ALLORESPONSES, International immunology, 10(1), 1998, pp. 71-83
In a model of heart allograft rejection in adult congeneic rats mismat
ched for both class I and class II MHC molecules, we analyzed the TCR
beta chain repertoire of T cells infiltrating rejected allografts [gra
ft-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 pro
cess, 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 lymphocy
te 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 b
etween BV2-BJ2S3 junctions derived from GITC in all individuals tested
and the presence of conserved amino acids at constrained CDR3 positio
ns within GITC BV13(+) junctions derived from most individuals. These
results suggest the existence of several major alloantigens responsibl
e for expansion of T cell clones bearing a 'public' beta chain rearran
gement 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.