THE T-CELL RECEPTOR GENE USAGE BY SIMIAN IMMUNODEFICIENCY VIRUS GAG-SPECIFIC CYTOTOXIC T-LYMPHOCYTES IN RHESUS-MONKEYS

MHC class I-restricted CTL play an important role in limiting the spre ad of HIV-1 in the infected individual. Elucidating the molecular inte ractions of CTL with the virus is, therefore, of central importance fo r characterizing the immune control of this infection. In exploring th is CTL response, we have defined the TCR usage by SIVmac Gag-specific CTL in rhesus monkeys. Thirty-nine CTL clones were generated from PBL of three SIVmac-infected monkeys expressing the MHC class I Mamu-A01 gene product, all of which were shown to recognize a single SIVmac Gag peptide in association with Mamu-A01. Sixty-six percent of CTL clone s derived from two monkeys early after infection expressed TCR genes o f the V beta 13 family; 70% of these V beta 13(+) CTL clones expressed a TCR heterodimer composed of V alpha 1 and V beta 13 gene products. In addition, there appeared to be a selection of a single conserved am ino acid and restricted CDR3 lengths in junctional regions of TCR beta -chains expressed by the V beta 13(+) CTL clones. These findings indic ate significant structural constraints on the CTL-TCR interaction with the AIDS virus, Interestingly, 55% of the CTL clones derived from the third animal at a later time following infection employed genes of th e V beta 6 family in their TCR, Despite the preferential use of TCR V family genes by the CTL clones, the SIVmac Gag-specific CTL response w as clearly polyclonal; TCR expressed by these CTL clones displayed var ied sequences in their CDR3 regions, Other V gene families, including V beta 23, V alpha 8, and V alpha 20, were used in TCR expressed by SI Vmac Gag-specific CTL clones. These studies, therefore, indicate that the TCR repertoire of SIVmac Gag-specific CTL that share a peptide and MHC class I recognition specificity can be diverse. Such a broad CTL- TCR repertoire may be advantageous for the host in containing an AIDS virus infection.