LAUSR

The expression of HLA alleles varies and can influence adaptive immune responses beyond the HLA peptide-presentation ability. In Science, Carrington and colleagues show that allelic variation that increases HLA-A expression results in an impaired ability to control infection with human immunodeficiency virus (HIV). Multi-study analyses of HIV-infected cohorts reveal a positive correlation between HLA-A expression and viral load and a reduced number of CD4+ T cells. HLA-A leader peptides are presented by HLA-E to form a ligand complex for the inhibitory receptor NKG2A expressed on natural killer cells. In vitro studies also show that impaired natural killer cell activity varies with the abundance of HLA-A expression, especially when combined with certain variants of HLA-B leader peptides. This suggests that blocking NKG2A–HLA-E interactions could be beneficial in combating HIV. LAD