To eliminate virally infected cells, cytotoxic T lymphocytes (CTLs) must recognize viral antigens that are properly displayed on the cell surface by a molecule called MHC class I. To escape the CTL-mediated killing, viruses have evolved a variety of mechanisms to dampen the antigen presenting functions of MHC class I. Interestingly, although the structure of the neonatal Fc receptor (FcRn) is very similar to the MHC class I, FcRn is unable to present antigens to T cells. In contrast, FcRn is capable of transporting IgG across epithelial cells and protecting IgG from degradation. In this way, FcRn ensures an effective and long-lasting antibody-mediated immunity after infection and vaccination. Given that FcRn and MHC class I molecules share a very closely similar structure, we hypothesize viruses must possess mechanisms to interfere with FcRn structure and function, consequently inhibiting important IgG functions during infection. By using a model pathogen human cytomegalovirus, we seek to fully investigate this possibility. Therefore, this study will potentially discover a novel immune evasion mechanism by hindering FcRn function. Consequently, this study will significantly improve our knowledge for the rational design of novel strategies for HCMV vaccine development and antibody-mediated passive immunization and immune therapy.
HCMV is the leading viral cause of congenital birth defects and cause severe diseases in the immunocompromised patients and organ transplanted recipients. FcRn transports IgG antibody and prolongs IgG half-life in the host. Understanding of the molecular mechanisms by which HCMV impairs FcRn functions may discover a novel mechanism of virus immune evasion and add new knowledge on IgG antibody-mediated immune therapy, passive immunization, and vaccine development.