DIFFERENTIAL IMMUNE RESPONSIVENESS TO THE IMMUNODOMINANT EPITOPES OF REGULATORY PROTEINS (TAX AND REX) IN HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE I-ASSOCIATED MYELOPATHY

Infection by human T cell lymphotropic virus type I (HTLV-I) is etiolo gically linked with HTLV-I-associated myelopathy (HAM) or adult T cell leukemia (ATL). To evaluate the contribution of the viral regulatory proteins tax and rex during the development of disease, antibody respo nses to these proteins were analyzed in patients with HAM (n = 28) or ATL (n = 48) and in asymptomatic carriers (n = 69). Epitope mapping an alysis identified immunodominant epitopes towards the amino terminus ( Tax8(106-125)) and at the carboxyl terminus (Tax22(316-335) Tax23(331- 350), and Tax24(336-353)) Of tax and the amino terminus (Rex1(1-20), R ex2(16-35), Rex4(46-65) and Rex6(76-95)) of rex. Analysis fanatically reactivity to these immunodominant epitopes demonstrated preferential reactivity to Tax8, Tax22, Tax23, and Tax24 (71%-93%) and to Rex4 and Rex6 (52%) in p8tients with HAM when compared with reactivities in ATL patients (4%-31% for tax and 19%-24% for rex) or asymptomatic carrier s (27%-37% for tax and 7%-23% for rex). In contrast, antibody response s to the immunodominant epitopes of the env proteins of HTLV-I (MTA, E nv1, Env5) were similar in all of three clinical groups. Thus, differe ntial immune responsiveness to the immunodominant epitopes of tax and rex in patients with HAM may play a role in disease pathogenesis in HT LV-I-infected persons.