Differential immune responsiveness to the immunodominant epitopes of regulatory proteins (tax and rex) in human T cell lymphotropic virus type I-associated myelopathy.

Abstract

Infection by human T cell lymphotropic virus type I (HTLV-I) is etiologically 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 responses to these proteins were analyzed in patients with HAM (n = 28) or ATL (n = 48) and in asymptomatic carriers (n = 69). Epitope mapping analysis 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), Rex2(16-35), Rex4(46-65), and Rex6(76-95)) of rex. Analysis of antibody reactivity to these immunodominant epitopes demonstrated preferential reactivity to Tax8, Tax22, Tax23, and Tax24 (71%-93%) and to Rex4 and Rex6 (52%) in patients with HAM when compared with reactivities in ATL patients (4%-31% for tax and 19%-24% for rex) or asymptomatic carriers (27%-37% for tax and 7%-23% for rex). In contrast, antibody responses to the immunodominant epitopes of the env proteins of HTLV-I (MTA, Env1, Env5) were similar in all of three clinical groups. Thus, differential immune responsiveness to the immunodominant epitopes of tax and rex in patients with HAM may play a role in disease pathogenesis in HTLV-I-infected persons.