Genetic Variants of Fcγ (GM Allotypes) and the Fc-Mediated Effector Functions in HIV-1 Controllers

Abstract

Genome-wide association studies (GWAS) have concluded that HLA class I alleles are the primary determinants of the outcome of HIV-1 infection. However, in a comprehensive analysis of the role of humoral immunity in HIV-1 control, Lai et al. (1) conclude that the “presence or absence of protective HLA alleles is not associated with strikingly divergent antibody responses” among HIV-1 controllers and that “understanding the specific features of IgGs with potentiated effector function may be critical to vaccine and therapeutic antibody development.” To explain the observed correlation between HIV-specific IgG1 antibodies and the total IgG1, the authors suggest that GM allotypes, hereditary antigenic variants of the immunoglobulin chains, may have influenced the baseline IgG subclass concentrations. I would like to add that GM allotypes, expressed primarily in the Fc region, may have contributed to all Fc-mediated effector functions listed by the authors: antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent complement-dependent cytotoxicity (ADCDC).