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 II0/0mice) or its associated invariant chain (Ii0/0mice) 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 Ii0/0and absent in class II0/0mice. 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 II0/0and up to threefold in Ii0/0mice. In class II0/0mice, the T-helper-independent neutralizing IgM response against the glycoprotein of VSV was within normal ranges but, in contrast to previous results on CD40/0mice, the T-helper-dependent IgG response was absent. Ii0/0mice exhibited a normal neutralizing IgM response; in contrast to class II0/0mice, 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 Ii0/0mice, 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 cellsin vivo.