LIMITED T-CELL RECEPTOR USAGE BY HTLV-I TAX-SPECIFIC, HLA CLASS-I RESTRICTED CYTOTOXIC T-LYMPHOCYTES FROM PATIENTS WITH HTLV-I-ASSOCIATED NEUROLOGICAL DISEASE

T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-spe cific, HLA class I restricted CD8(+) cytotoxic T cells (CTL) was deter mined from lymphocytes obtained from peripheral blood of patients with HTLV-I associated neurological disease. To characterize TCR repertoir e, CD8(+) lymphocytes from peripheral blood were cloned in limiting di lution, and the resulting wells were screened for HTLV-I-specific prec ursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I tax peptide-specific (tax 11-19; LLFGYPVYV) CD8(+) CTL lines and cDNA was analyzed by PCR amplification using Ver and VP chain family-specific oligonucleotide primers. The results indicate that CD8(+) cytotoxic T cell lines from HLA-A2 HAM/TSP patients express a limited repertoire o f T cell receptor chains which may correlate with duration and severit y of disease. The restricted use of TCR genes expressed by antigen-spe cific CTL may play a critical role in the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic strategies that focus on eliminating these cells or inhibiting their activity.