Antiviral immune responses of mice lacking MHC class II or its associated invariant chain

Induction of T-helper cells and T-B cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (MHC) class II molecules by the T cell receptor. Mice lacking either MHC class II molecules (class II0/0 mice) or its associated invariant chain (Ii(0)/0 mice) provide new opportunities to test this premise. Immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. We therefore tested CD8(+) effector T cells and CD4(+) T-cell-dependent B cell function during different viral infections. The vesicular stomatitis virus (VSV)-specific primary cytotoxic T cell response which is largely T-helper-dependent was diminished in Ii(0)/0 and absent in class II0/0 mice. The usually less T-helper-dependent cytotoxic vaccinia or lymphocytic choriomeningitis virus (LCMV)-specific CD8(+) T cell responses were reduced up to ninefold in class II0/0 and up to threefold in Ii(0)/0 mice. In class II0/0 mice, the T-helper-independent neutralizing IgM response against the glycoprotein of VSV was within normal ranges but, in contrast to previous results on CD4(0)/0 mice, the T-helper-dependent IgG response was absent, Ii(0)/0 mice exhibited a normal neutralizing IgM response; in contrast to class II0/0 mice, they mounted a significant, though reduced specific IgG response. Similar results were obtained for antibody responses against the nucleoprotein of VSV. Although the T-helper-cell response upon infection with VSV seemed diminished only a little in Ii(0)/0 mice, presentation of VSV-G to a class II-restricted specific hybridoma was greater than 300-fold reduced in the absence of Ii. This suggests that local protein concentrations reached during viral infection in the host are high enough to override the Ii deficiency of antigen-presenting cells in vivo. (C) 1996 Academic Press, Inc.