NATURALLY-OCCURRING VARIANTS OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I TAX PROTEIN IMPAIR ITS RECOGNITION BY CYTOTOXIC T-LYMPHOCYTES AND THE TRANSACTIVATION FUNCTION OF TAX

There is a high degree of intraisolate sequence heterogeneity in the t ax gene of human T-cell leukemia virus type I (HTLV-I), although the s equence variation between patients is small compared with that of huma n immunodeficiency virus type 1. In the present study, we investigated whether naturally occurring amino acid substitutions changed the prop erties of the Tax protein in two respects: first, recognition of the p rotein by cytotoxic T lymphocytes (CTL), and second, the ability of th e Tax protein to transactivate various promoters. We found that (i) al l of the observed amino acid substitutions that occur in known CTL epi topes abolished the recognition of the synthetic peptide representing the respective epitope; (ii) these substitutions occurred significantl y more frequently in subjects carrying HLA-A2; and (iii) most of the a mino acid substitutions severely reduced the ability of Tax protein to transactivate three promoters: the HTLV-I long terminal repeat, the c -fos promoter, and the interleukin-2 receptor alpha chain promoter.