HLA-DQB1*06 and breadth of Nef core region-specific T-cell response are associated with slow disease progression in antiretroviral therapy-naive Chinese HIV-1 subtype B patients

Abstract

Vaccines still are an important way to prevent and treat acquired immunodeficiency syndrome (AIDS). ¹ For developing an effective T cell-based AIDS vaccine, it is critical to define the human leukocyte antigen (HLA) type and epitope that elicit the most potent responses. This study involved 29 antiretroviral therapy-naive and chronic human immunodeficiency virus (HIV)-1 subtype B-infected individuals. A polymerase chain reaction-sequence-specific primer was used to detect the HLA typing, and the enzyme-linked immunospot assay to quantify the T-cell immune function. The results showed that the HLA-DQB1*06-positive group had higher CD4 counts and lower viral load (VL) compared with the HLA-DQB1*06-negative group; A higher magnitude of HIV-1-specific T-cell response and breadth were observed in the HLA-DQB1*06-positive group; the T-cell response was proportional to VL (R² = 0.488, P = 0.0368) in the HLA-DQB1*06-positive group. The total T-cell responses to HIV-1 Nef core region were quantified at the single-peptide level. Nine (90%) peptides were recognized in 18 (62.1%) individuals. The breath of Nef core region-specific T-cell response was correlated positively with CD4⁺ T cell count and inversely with VL, which improved disease outcomes. These data revealed that HLA-DQB1*06 had a protective effect on the course of HIV-1 and T-cell targeting of certain specific Nef epitopes, contributing to HIV-1 suppression. The results suggested the potential use of HLA-DQB1*06 and Nef core region in HIV-1 T-cell vaccine design.

Keywords: HIV-1; HLA; NEF T-cell response; Vaccine.

Figure 1.

Magnitude of human immunodeficiency virus (HIV)-1 subtype B Nef core specific T cell responses in 29 HIV-1B-infected individuals. Measured as interferon (IFN)-γ enzyme-linked immunospot (ELISPOT), represented as spot-forming units (SFU)/10⁶ peripheral blood mononuclear cells.

Figure 2.

Magnitude and frequency of 10 HIV-1 subtype B Nef core OLPs. The total magnitude of T cell responses specific for each tested peptide is shown as bars in the left part of the graph. The frequency of each tested peptide is shown as bars on the right part of the graph.

Figure 3.

The heatmap for all patients and all peptides provide full picture with the ELISPOT responses. The right ordinate is the patient NO., The bottom abscissa is the peptide NO. The heatmap should define the cut-off as the detection limit.

Figure 4.

ELISPOT magnitude is associated with CD4⁺T cell count and viral load. The associations between ELISPOT magnitude (total spot forming units per 1 Million PBMCs and CD4⁺T cell count or viral load) were analyzed by Spearman's correlation. The Nef core-specific response was compared with CD4⁺T cell count (a) and viral load (b). P value is corrected by FDR.

Figure 5.

ELISPOT breadth is associated with CD4⁺T cell countand viral load. The associations between ELISPOT breadth [the number of reacting OLPs] and CD4⁺T cellcount (a) or viral load (b) were analyzed using the Kruskal-Wallis test. (n) Refers to the number of individuals. P value is corrected by FDR.

Figure 6.

Comparison of CD4 count, VL, Magnitude and Breadth between DQB1*06 positive and negative group. P value is corrected by FDR.

Figure 7.

DQB1*06 allele-specific enzyme-linked immunospot (ELISPOT) magnitude were compared with viral load (VL) and CD4+ T cell count. P value is corrected by FDR.