Biased TCR repertoire in HIV-1-infected patients due to clonal expansion of HIV-1-reverse transcriptase-specific CTL clones

To study whether an expansion of HIV-l-specific CTL is contributing to the skewed TCR repertoire in HIV-l-infection, we characterized the TCR usage of CTL clones specific for a conserved epitope in HIV-1 reverse transcriptase (RT/476-484), CTL clones from three HIV-l-infected patients displayed high ly similar TCR usage and used the identical V beta 6.1 and V alpha 2.5 gene segments. CTL clones from two patients showed a very high degree of simila rity within the TCR complementarity-determining region-3 (CDR-3). In accord ance with the similar molecular structure, all three CTL clones also exhibi ted a similar functional activity with regard to recognition of variant pep tides and cytokine secretion pattern. In one subject clonal expansion of a single CTL specificity could be shown over a 10-mo period. TCR spectratypin g of PBMC from two patients revealed a marked expansion of CDR-3 segments o f a certain length within the V beta 6-family. Sequence analysis of these C DR-3 yielded sequences identical to the RT/476-484-specific CTL previously isolated from the same patients. This analysis demonstrates that clonal exp ansion of HIV-1-specific CTL is contributing to the skewed TCR repertoire i n HIV-1-infected patients.