VIRUS-SPECIFIC, CD8(-RESTRICTED CYTOTOXIC T-LYMPHOCYTES IN LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTED BETA(2)-MICROGLOBULIN-DEFICIENT MICE() MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I)

Following infection with lymphocytic choriomeningitis virus (LCMV), no rmal adult mice generate virus-specific, major histocompatibility comp lex (MHC) class I-restricted cytotoxic T lymphocytes (CTL) which clear the virus after intraperitoneal infection or cause death following in tracranial (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 g enerate CD4(+) MHC class II-restricted CTL in response to LCMV, KOD mi ce generate high levels of CD8(+) MHC class I-restricted, virus-specif ic CTL. These CTL are specific for the LCMV nucleoprotein epitope (res idues 118 to 126) in association with the L-d class I molecule, analog ous to the CTL response in wild-type mice. KOD mice are also susceptib le 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 m ice, 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 mi ce, however, KOD mice cannot control LCMV and become persistently infe cted. Overall, these results demonstrate that beta(2)m is not an absol ute requirement for presentation of endogenous antigen on L-d or for i nduction of virus-specific L-d-restricted CTL in vivo.