T-CELL RECEPTOR GENES IN A SERIES OF CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-RESTRICTED CYTOTOXIC LYMPHOCYTE-T CLONES SPECIFIC FOR A PLASMODIUM-BERGHEI NONAPEPTIDE - IMPLICATIONS FOR T-CELL ALLELIC EXCLUSION AND ANTIGEN-SPECIFIC REPERTOIRE

We report here the first extensive study of a T cell repertoire for a class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocyte (CTL) response. We have found that the T cell receptors (TCRs) carried by 28 H-2K(d)-restricted CTL clones specific for a single Plasmodium berghei circumsporozoite nonapeptide are highly diverse in terms of V-alpha, J-alpha, and J-beta segments and aminoacid composition of the junctional regions. However, despite this extensive diversity, a high proportion of the TCRs contain the same V-beta segment. These results are in contrast to most previously reported T cell responses towards class II MHC-peptide complexes, where the TCR repertoires appeared to be much more limited. In our study, the finding of a dominant V-beta in the midst of otherwise highly diverse TCRs suggests the importance of the V-beta segment in shaping the T cell repertoire specific for a given MHC-peptide complex. As an additional finding, we observed that nearly all clones have rearranged both TCR alpha-loci. Moreover, as many as one-third of the CTL clones that we analyzed apparently display two productive ce rearrangements. This argues against a regulated model of sequential recombination at the alpha-locus and consequently raises the question of whether allelic exclusion of the TCR alpha-chain is achieved at all.