Effect of human leukocyte antigen homozygosity on rubella vaccine–induced humoral and cell-mediated immune responses

Human leukocyte antigen (HLA) genes play a critical role in host immunity, including vaccine responses. HLA molecules present antigenic peptides to T cells and provide inhibitory signals to NK cells, and polymorphisms within HLA genes allow binding and presentation of a diverse array of self and foreign peptides. Heterozygosity across HLA alleles has been found to play a positive role in host defense for a variety of infections. Homozygosity within one or more HLA loci may restrict this epitope repertoire and limit T-cell responses to infection or vaccination. Here we report that homozygosity within the HLA DPB1 locus is associated with increased levels of rubella-specific IgG, an effect driven by a common allele DPB1*0401. We also show that homozygosity within different HLA class I and class II loci is correlated with variations (but not necessarily decreases) in interleukin (IL)–2, IL-5, and IL-10 secretion after rubella virus stimulation.