Protective HLA Alleles Recruit Biased and Largely Similar Antigen-Specific T Cell Repertoires across Different Outcomes in HIV Infection

Abstract

CD8⁺ T cells play an important role in the control of untreated HIV infection. Several studies have suggested a decisive role of TCRs involved in anti-HIV immunity. HLA-B*27 and B*57 are often associated with a delayed HIV disease progression, but the exact correlates that provide superior immunity against HIV are not known. To investigate if the T cell repertoire underlies the protective effect in disease outcome in HLA-B*27 and B*57⁺ individuals, we analyzed Ag-specific TCR profiles from progressors (n = 13) and slow progressors (n = 11) expressing either B*27 or B*57. Our data showed no differences in TCR diversity between progressors and slow progressors. Both alleles recruit biased T cell repertoires (i.e., TCR populations skewed toward specific TRBV families or CDR3 regions). This bias was unrelated to disease progression and was remarkably profound for HLA-B*57, in which TRBV family usage and CDR3 sequences were shared to some extent even between epitopes. Conclusively, these data suggest that the T cell repertoires recruited by protective HLA alleles are highly similar between progressors and slow progressors in terms of TCR diversity, TCR usage, and cross-reactivity.