Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells. Science
The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference.
Ramsuran et al. examined data from 9’763 HIV-infected individuals from 21 cohorts. They found that higher HLA-A levels confer poorer control of HIV.
Expression of the HLA-A and -B alleles was associated with:
– higher viral load
– reduced CD4+ T cell counts
– accelerated progression to AIDS.
Higher levels of HLA-A expression increased expression of HLA-E, which blocks a specific receptor (NKG2A) on the immune cells that normally eliminate virus-infected cells.
In conclusion, the data suggest that antagonizing HLA-E/NKG2A interactions, perhaps in combination with other therapies, may provide benefit in HIV disease. This might be an attractive approach in HIV cure strategies. Genetic validation of NKG2A as a therapeutic target in additional diseases by testing for effects of HLA-A and HLA-B –21 genotypes may rationalize the use of anti-NKG2A therapy in other disorders.