Roles of Major Histocompatibility Complex Class II in Inducing Protective Immune Responses to Influenza Vaccination

Major histocompatibility complex class II-deficient (MHC-II KO; A/) mice were used to assess the roles of MHC-II mole-cules in inducing protective immune responses to vaccination. After vaccination with influenza A/PR8 virus-like particle (VLP) vaccine, in vivo and in vitro vaccine antigen-specific IgG isotype antibodies were not detected in MHC-II KOmice, which is quite different from CD4 T cell-deficient mice that induced vaccine-specific IgG antibodies. The deficiency inMHC-II did not significantly affect the induction of antigen-specific IgM antibody in sera. MHC-II KOmice that were vaccinated with influenza VLP, whole inactivated influenza virus, or live attenuated influenza virus vaccines were not protected against lethal infection with influenza A/PR8 virus. Adoptive transfer of fractionated spleen cells fromwild-type mice toMHC-II KOmice indicated that CD43 cell populations withMHC-II contributed more significantly to producing vaccine-specific IgG antibodies than CD43 B220 conventional B cell or CD4 T cell populations, as well as conferring protection against lethal infection. Bone marrow-derived dendritic cells fromMHC-II KOmice showed a significant defect in producing interleukin-6 and tumor necrosis factor alpha cytokines. Thus, results indicate that MHC-II molecules play multiple roles in inducing protective immunity to influenza vaccination. IMPORTANCE Major histocompatibility complex class II (MHC-II) has been known to activate CD4 T helper immune cells. A deficiency i