Virus-specific, CD8⁺ major histocompatibility complex class I- restricted cytotoxic T lymphocytes in lymphocytic choriomeningitis virus- infected β₂-microglobulin-deficient mice

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 β₂-microglobulin-deficient (β₂m^-) mice of the H-2(d) haplotype (KOD mice) to LCMV infection. Unlike H-2(b) β₂m^- 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 β₂m 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.