HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors

TLDR

The study aims to characterize qualitative differences in virus‑specific immune responses between HLA B*57+ long‑term nonprogressors and progressors to elucidate mechanisms of effective viral restriction. Researchers recruited a cohort of HIV‑1‑infected long‑term nonprogressors with normal CD4⁺ counts and <50 copies/mL plasma and quantified antigen‑specific CD8⁺ T cells by flow cytometry of intracellular IFN‑γ and HLA B*57‑gag tetramer staining. HLA B*5701 is strongly associated with nonprogressive infection (85 % of B*57⁺ LTNPs versus 9.5 % of progressors), and although total HIV‑specific CD8⁺ T‑cell responses are comparable, LTNPs display a gag‑specific CD8⁺ T‑cell response focused on B*57‑restricted peptides, indicating that B*5701 mediates virus‑specific immune restriction.

Abstract

A unique cohort of HIV-1-infected long term nonprogressors (LTNP) with normal CD4(+) T cell counts and <50 copies/ml of plasma were prospectively recruited for study. HLA typing revealed a dramatic association between the HLA B*5701 class I allele and nonprogressive infection [85% (11 of 13) vs. 9.5% (19 of 200) in progressors; P < 0. 001]. Antigen-specific CD8(+) T cells were enumerated by flow cytometric detection of intracellular IFN-gamma in response to HIV antigens and HLA B*57-gag tetramer staining. No quantitative differences in the total HIV-specific CD8(+) T cell responses were observed between B*57(+) LTNP and five B*57(+) progressors (P = 0.4). Although similar frequencies of peptide specific CD8(+) T cells were also found, the gag-specific CD8(+) T cell response in the LTNP group was highly focused on peptides previously shown to be B*57-restricted. These findings indicate that, within this phenotypically and genotypically distinct cohort, a host immune factor is highly associated with restriction of virus replication and nonprogressive disease. They also strongly suggest a mechanism of virus specific immunity that directly operates through the B*5701 molecule. Further characterization of qualitative differences in the virus-specific responses that distinguish HLA B*57(+) LTNP from progressors may ultimately define mechanisms of effective immune mediated restriction of virus replication.