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). 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 (R = 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.

An atlas of immune cell transcriptomes in human immunodeficiency virus-infected immunological non-responders identified marker genes that control viral replication

“…[ 30 ] HLA-DQB106 , a variant allele of the HLA-DQB1 gene, has been found to play a protective role against HIV-1 disease progression and the targeting of T cells by specific Nef epitopes, thereby contributing to the suppression of HIV-1 replication. [ 31 ] Individuals with the strongest HIV-specific CD4 + T-cell responses commonly carry HLA class II gene-specific alleles, such as HLA-DRB113 and/or HLA-DQB106 , which have previously been associated with non-progressive HIV infection phenotypes. [ 32 ] This indicates that HLA-DQB106 plays an important and positive role in the regulation of the immune response to HIV-1 infection.…”

Association between Human Leukocyte Antigen (HLA) DQB1*06 and HLA DQB1*03 and adverse outcomes in a group of critically ill patients with COVID-19 in Tunisia: a cross-sectional study

“…A Chinese study also found that HLA DQB1*06 had protective effect on the evolution of HIV infection and T-cell targeting of specific HIV Nef epitopes. This study even proposes the consideration of the presence of HLA DQB1*06 in the production of the anti-HIV vaccine, given the role of this allele in the promotion of specific anti-HIV lymphocyte immune response [ 24 ]. Regarding Epstein Barr Virus (EBV) infection, it was found that people homozygous for HLA DQB1*06 were more likely to be EBV seronegative than other DQB1 combinations [ 23 ].…”

The roles of HLA-DQB1 gene polymorphisms in hepatitis B virus infection

“…Several polymorphisms in the HLA loci, especially HLA-II, are related to HBV infection susceptibility or spontaneous HBV clearance [6–10]. Furthermore, HLA-DQB1 gene polymorphisms are associated with the progression of human immunodeficiency virus infection [11], HCV infection susceptibility and spontaneous clearance [12], coronary artery disease [13], rheumatoid arthritis [14], and other diseases.…”