Abstract

Following infection with lymphocytic choriomeningitis virus (LCMV), normal adult mice generate virus-specific, major histocompatibility complex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) which clear the virus after intraperitoneal infection or cause death following intracranial (i.c.) infection. We have investigated the response of beta(2)-microglobulin-deficient (beta(2)m(-)) mice of the H-2(d) haplotype (KOD mice) to LCMV infection. Unlike H-2(b) beta(2)m(-) mice, which generate CD4(+) MHC class II-restricted CTL in response to LCMV, KOD mice generate high levels of CD8(+) MHC class I-restricted, virus-specific CTL. These CTL are specific for the LCMV nucleoprotein epitope (residues 118 to 126) in association with the L-d class I molecule, analogous to the CTL response in wild-type mice. KOD mice are also susceptible to lethal LCM disease, with 75 to 80% of the mice dying 7 to 9 days following i.c. infection with virus. Similar to results with normal mice, lethal LCM disease in KOD mice is prevented by in vivo depletion of CD8(+) T cells prior to i.c. infection. In contrast to wild-type mice, however, KOD mice cannot control LCMV and become persistently infected. Overall, these results demonstrate that beta(2)m is not an absolute requirement for presentation of endogenous antigen on L-d or for induction of virus-specific L-d-restricted CTL in vivo.