IMPAIRED INDUCTION OF CYTOTOXIC T-LYMPHOCYTES BY ANTAGONISM OF A WEAKAGONIST BORNE BY A VARIANT HEPATITIS-C VIRUS EPITOPE

An epitope that acted as a weak agonist in the cytotoxicity assay was identified as part of the capsid protein of a hepatitis C virus (HCV) variant. In a low concentration, the variant epitope also had a weak a ntagonistic effect. When a minute amount of this variant epitope was a dded to the culture for induction, it selectively attenuated the expan sion of major cytotoxic T cell populations and drastically reduced the cytotoxic responses against the wild-type epitope. Thus, antagonism t o induction suppressed immune responses against both the wild type and the variant, thereby helping the persistence of not only variant itse lf but also the wild-type HCV. Because this variant was a weak agonist , most cytotoxic T cells induced with the wild-type epitope were cross -reactive with the variant and susceptible to the antagonism to induct ion. Only the T cells which were not cross-reactive with the variant a nd not susceptible to the antagonism survived the antagonism in induct ion. This implied that the specificity of the remaining immune respons e, if any, was directed exclusively to the wild-type epitope after the emergence of the variant. For viruses like HCV, being heterogeneous i tself may contribute significantly toward persistent infection through antagonism to induction.