Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection.

Abstract

A transgenic mouse expressing MHC class II-restricted TCR with specificity for a lymphocytic choriomeningitis virus (LCMV) glycoprotein-derived T helper cell epitope was developed to study the role of LCMV-specific CD4+ T cells in virus infection in vivo. The majority of CD4+ T cells in TCR transgenic mice expressed the transgenic receptor, and LCMV glycoprotein-specific TCR transgenic CD4+ T cells efficiently mediated help for the production of LCMV glycoprotein-specific isotype-switched antibodies. In contrast, LCMV glycoprotein-specific TCR transgenic mice exhibited a drastically reduced ability to provide help for the generation of antibody responses specific for the virus-internal nucleoprotein, indicating that intramolecular/intrastructural help is limited to antigens that are accessible to B cells on the viral surface. Antiviral cellular immunity was studied with noncytopathic LCMV and recombinant cytopathic vaccinia virus expressing the LCMV glycoprotein. TCR transgenic mice failed to efficiently control LCMV infection, demonstrating that functional LCMV-specific CD4+ T cells--even if activated and present at extremely high frequencies--cannot directly mediate protective immunity against LCMV. Despite the fact that LCMV-primed CD4+ T cells from TCR transgenic mice as well as from control mice showed low MHC class II-restricted cytotoxic activity in vivo, this did not correlate with protection against LCMV replication in vivo. In contrast, CD4+ T cells from TCR-transgenic mice mediated efficient protection against infection with recombinant vaccinia virus. These results further support the need for different immune effector functions for protective immunity against different viral infections.