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

Hum Vaccin Immunother. 2017 Oct 3;13(10):2341-2347. doi: 10.1080/21645515.2017.1340138.

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.

MeSH terms

  • AIDS Vaccines
  • Adult
  • Antiretroviral Therapy, Highly Active
  • Asian People
  • CD4 Lymphocyte Count
  • CD8-Positive T-Lymphocytes / immunology
  • Disease Progression
  • Drug Design
  • Enzyme-Linked Immunospot Assay
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / ethnology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / classification
  • HIV-1 / immunology*
  • HLA-DQ beta-Chains / genetics
  • HLA-DQ beta-Chains / immunology*
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic / immunology
  • Viral Load
  • Young Adult
  • nef Gene Products, Human Immunodeficiency Virus / chemistry
  • nef Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • Epitopes, T-Lymphocyte
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1