Rapid progressing allele HLA-B35 Px restricted anti-HIV-1 CD8+ T cells recognize vestigial CTL epitopes

Abstract

Background: The HLA-B*35-Px allele has been associated with rapid disease progression in HIV-1 infection, in contrast to the HLA-B*35-Py allele.

Methodology/principal findings: Immune responses to two HLA-B*35 restricted HIV-1 specific CTL epitopes and their variants were followed longitudinally during early HIV-1 infection in 16 HLA-B*35+ individuals. Subjects expressing HLA-B*35-Px alleles showed no difference in response to the consensus epitopes compared to individuals with HLA-B*35-Py alleles. Surprisingly, all the HLA-B*35-Px+ individuals responded to epitope-variants even in the absence of a consensus response. Sequencing of the viral population revealed no evidence of variant virus in any of the individuals.

Conclusions/significance: This demonstrates a novel phenomenon that distinguishes individuals with the HLA-B*35-Px rapid progressing allele and those with the HLA-B*35-Py slower progressing allele.

Figure 1. A representative example, from subject 1, of longitudinal CD8+ T cell IFN-γ responses to the TY9 epitope (solid green bars) and VY10 (solid orange bars).

All subjects showed similar responses towards both epitopes that waxed and waned over the course of the study window.

Figure 2. CD8+ T cell IFN-γ responses to both consensus epitopes (solid bars, TY9 green and VY10 orange), and variant epitopes (TY9 variants green, checkered or stripped bars, and VY10 variant orange checkered bars).

Representative examples of longitudinal responses are shown for HLA-B*35 -Px+ Subjects 1 (A) and 2 (B), and HLA-B*35 -Py+ Subject 8 (C). CD8+ T cell IFN-γ responses from Subject 6, who expressed both HLA-B*35 -Px and -Py alleles (D). HLA-B*35 -Px+ individuals did not display unusual CD4 counts or viral loads, a representative example shown from Subject 1 (E).