VIRUS-SPECIFIC MHC CLASS II-RESTRICTED TCR-TRANSGENIC MICE - EFFECTS ON HUMORAL AND CELLULAR IMMUNE-RESPONSES AFTER VIRAL-INFECTION

A transgenic mouse expressing MHC class Ii-restricted TCR with specifi city for a lymphocytic choriomeningitis virus (LCMV) glycoprotein-deri ved T helper cell epitope was developed to study the role of LCMV-spec ific 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 tran sgenic mice exhibited a drastically reduced ability to provide help fo r 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 surfa ce. Antiviral cellular immunity was studied with noncytopathic LCMV an d recombinant cytopathic vaccinia virus expressing the LCMV glycoprote in. TCR transgenic mice failed to efficiently control LCMV infection, demonstrating that functional LCMV-specific CD4(+) T cells - even if a ctivated and present at extremely high frequencies - cannot directly m ediate protective immunity against LCMV, Despite the fact that LCMV-pr imed CD4(+) T cells from TCR transgenic mice as well as from control m ice showed low MHC class II-restricted cytotoxic activity in vivo, thi s did not correlate with protection against LCMV replication in vivo. In contrast, CD4(+) T cells from TCR-transgenic mice mediated efficien t protection against infection with recombinant vaccinia virus. These results further support the need for different immune effector functio ns for protective immunity against different viral infections.