Roles of major histocompatibility complex class II in inducing protective immune responses to influenza vaccination

• Published in: Journal of virology 2014-07, Vol.88 (14), p.7764-7775
• Main Authors: O, Eunju, Lee, Young-Tae, Ko, Eun-Ju, Kim, Ki-Hye, Lee, Yu-Na, Song, Jae-Min, Kwon, Young-Man, Kim, Min-Chul, Perez, Daniel R, Kang, Sang-Moo
• Format: Article
• Language: English
• Subjects: Adoptive Transfer; Animals; Antibodies, Viral - blood; Female; Histocompatibility Antigens Class II - analysis; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - immunology; Immunoglobulin G - blood; Immunoglobulin M - blood; Influenza A virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - immunology; Influenza virus; Leukocytes, Mononuclear - chemistry; Leukocytes, Mononuclear - immunology; Leukosialin - analysis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Vaccines and Antiviral Agents; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - immunology; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - immunology; Vaccines, Virus-Like Particle - administration & dosage; Vaccines, Virus-Like Particle - immunology
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/JVI.00748-14

Major histocompatibility complex class II-deficient (MHC-II KO; Aβ(-/-)) mice were used to assess the roles of MHC-II molecules 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 KO mice, which is quite different from CD4 T cell-deficient mice that induced vaccine-specific IgG antibodies. The deficiency in MHC-II did not significantly affect the induction of antigen-specific IgM antibody in sera. MHC-II KO mice 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 from wild-type mice to MHC-II KO mice indicated that CD43(+) cell populations with MHC-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 from MHC-II KO mice 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 in MHC-II was considered to be equivalent to the lack of CD4 T cells in developing host immune responses to pathogens. However, the roles of MHC-II in inducing protective immune responses to vaccination have not been well understood. In the present study, we demonstrate that MHC-II-deficient mice showed much more significant defects in inducing protective antibody responses to influenza vaccination than CD4 T cell-deficient mice. Further analysis showed that CD43 marker-positive immune cells with MHC-II, as well as an innate immunity-simulating adjuvant, could rescue some defects in inducing protective immune responses in MHC-II-deficient mice. These results have important implications for our understanding of host immunity-inducing mechanisms to vaccination, as well as in developing effective vaccines and adjuvants.