Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression in HLA-A*30-B*13-C*06-positive patients

Zhang, Hui; Han, Xiaoxu; Zhao, Bin; An, Minghui; Wang, Zhe; Jiang, Fanming; Xu, Junjie; Zhang, Zining; Dong, Tao; Shang, Hong

doi:10.1097/qad.0000000000000652

Cited by 8 publications

(14 citation statements)

References 35 publications

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“…et al . showed that HLA‐A ∗ 30‐B ∗ 13‐C ∗ 06 contributes to the slow progression of HIV infection in the northern Chinese (Zhang et al, ). Three associated alleles, HLA‐C*08:01, C*08:04 and B*13:01 showed different frequencies in Yunnan Han population: HLA‐B*46:01, B*40:01 and B*13:01 were the most predominant alleles at HLA‐B locus; however, HLA‐C*08:01 and C*08:04 were only with frequencies about 4% (Shen et al, ).…”

Section: Discussionmentioning

confidence: 99%

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

Liu

Zhang

et al. 2019

Int J Immunogenetics

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The host immune system plays a key role in the elimination of infected cells which depend on killer‐cell immunoglobulin‐like receptors (KIR), human leucocyte antigen (HLA) class I molecules and their combinations. To evaluate the roles of HLAclass I, KIR genes and their combination in Chronic hepatitis C virus (HCV) infection (CHC), a total of 301 CHCs and 239 controls in a Chinese Han population were included for HLA and KIR genotyping using next‐generation sequencing and multiplex PCR sequence‐specific priming, respectively. The allele frequency of HLA‐C*08:01 was significantly higher in the CHCs than that of the controls (0.088 vs. 0.040, OR = 2.332, 95%CI: 1.361–3.996, p = 0.022), while the frequencies of B*13:01 (0.032 vs. 0.084, OR = 0.357, 95%CI: 0.204–0.625, p = 0.009) and C*08:04 (0.008 vs. 0.038, OR = 0.214, 95%CI: 0.079–0.581, p = 0.022) were significantly lower in the CHCs. The frequencies of haplotype A*11:01‐C*08:01 were higher in the CHCs (0.058 vs. 0.019, OR = 3.096, 95%CI: 1.486–6.452, p = 0.026), while haplotype B*13:01‐C*03:04 were lower in the CHCs compared to the controls (0.028 vs. 0.071, OR = 0.377, 95%CI: 0.207–0.685, p = 0.012). No association of CHC with KIR genes, genotypes, or haplotypes, as well as HLA/KIR combinations was observed. Our results indicated that HLA‐C*08:01 was a risk factor for CHC, while HLA‐C*08:04 and HLA‐B*13:01 were protective factors against CHC. Haplotypes HLA‐A*11:01‐C*08:01 could increase susceptibility to CHC, while HLA‐B*13:01‐C*03:04 could be protective against CHC in the Chinese Han population.

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Section: Discussionmentioning

confidence: 99%

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

Liu

Zhang

et al. 2019

Int J Immunogenetics

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“…Peripheral blood mononuleated cells (PBMCs) were isolated from the blood with Lymphoprep (STEMCELL Technologies , origin ). Interferon-γ (IFN-γ) ELISPOT assay was used to measure HPV E1-specific T cell responses in the freshly isolated PBMCs as mentioned previously [ 16 , 20 ]. Briefly, PBMCs were stimulated with overlapping peptide pool (Sigma-Aldrich, USA) representing the whole E1 protein in PVDF plates (Millipore, Bedford, MA, USA) pre-coated with 1-DIK monoclonal antibodies (Machete, Stockholm, Sweden) at 2 × 10 5 PBMCs/well.…”

Section: Methodsmentioning

confidence: 99%

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

Fan

et al. 2018

Infect Agents Cancer

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BackgroundCervical cancer is attributable to human papilloma virus (HPV) infection in the majority cases. E1, an HPV derived-protein, plays an important role in the initiation and development of cervical cancer. Our study aims to investigate the HPV E1-specific T cell response in patients with cervical squamous cell carcinoma (CSCC).MethodsA total of 66 CSCC patients with FIGO stage IIB-IIIB and 60 healthy controls were enrolled. Enzyme-Linked ImmunoSpot (ELISPOT) assays was used to measure the HPV E1-specific T cell response in the peripheral blood of these patients before treatment. The patients were treated with chemotherapy and/or radiotherapy and followed up clinically for three years. The relationship between the T cell response, various clinical characteristics and the prognosis were studied with univariate analysis, multivariate analysis and survival curve analysis.ResultsThe frequency of HPV E1-specific T cell response in peripheral blood of cervical cancer patients was 59.09%, with mean response intensity 24.56 SFC/106 PBMCs. The frequency and intensity of HPV E1-specific T cell response in patients were higher than healthy controls(p < 0.001; p = 0.009). The intensity of HPV E1-specific T cell responses were higher in the stage IIB patients and patients with no pelvic lymph node metastasis (p = 0.038; p = 0.044). Univariate analysis showed that HPV E1 specific T cell response was associated with progression-free survival (PFS) and overall survival (OS) (PFS: p = 0.021; OS: p = 0.004). Multivariate analysis showed that HPV E1-specific T cell response was an independent prognostic factor influencing PFS and OS among all the factors included in our study (PFS: HR = 7.252, 95%CI = 1.690–31.126, p = 0.008; OS: HR = 7.499, 95%CI = 1.661–33.856, p = 0.009). The survival curves showed that the rate of PFS and OS in patients with HPV E1 specific T cell response was significantly higher than those who did not response.ConclusionsOur study demonstrated that the level of HPV E1-specific T cell response was correlated with the survival of advanced patients with CSCC. Patients who displayed no HPV E1-specific T cell response were more likely to be those with poor prognosis.

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“…IFN-γ enzyme-linked immunospot (ELISPOT) assays were performed as previously described [ 36 ]. In brief, PBMCs were plated in 96-well plates that were precoated with anti-IFN-γ monoclonal antibody at 100,000 cells per well with peptides at a final concentration of 5 μg/ml for pooled peptides, single peptides, and optimal epitopes (BD TM ELISPOT, USA).…”

Section: Methodsmentioning

confidence: 99%

“…Viral RNA was extracted from plasma samples obtained from MSM subjects with the QIAamp Viral RNA Mini-kit (Qiagen, UK). The Gag gene was amplified using the SuperScript Polymerase One-Step RT-PCR System (Takara, Dalian, China), followed by a second round of PCR with Gag-specific primers [ 36 ]. PCR products were gel purified with the QIAquick gel extraction kit (Qiagen, UK) and cloned with a TOPO TA cloning kit (Invitrogen, USA).…”

Section: Methodsmentioning

confidence: 99%

Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects

et al. 2016

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BackgroundThe purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution.ResultsFifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma. Gag and Nef proteins were the main targets of CTL responses during the first year of HIV-1 infection, and this was evident from the data after adjusting for the length of amino acids by dividing the amino acids number of the corresponding protein and multiplying by 100. Additionally, relative magnitudes of Gag at both 3 months and 1 year post infection were significantly negatively correlated with the viral set point (p = 0.002, r = −0.726; p = 0.025, r = −0.574). While the relative magnitude of Nef at 1 year post infection were significantly positively correlated with viral set point (p = 0.004, r = 0.697). Subjects with multi-layered Gag immunodominant responses during the first year of infection had significantly lower viral set points than subjects without such responses (p = 0.002).ConclusionMulti-layered Gag immunodominant responses during the first year of infection were correlated with viral control, which provides a theoretical basis for vaccine design targeting MSM subjects with the CRF01_AE subtype.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0166-8) contains supplementary material, which is available to authorized users.

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Multilayered HIV-1 gag-specific T-cell responses contribute to slow progression in HLA-A30-B13-C*06-positive patients

Cited by 8 publications

References 35 publications

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

Human leucocyte antigen but not KIR alleles and haplotypes associated with chronic HCV infection in a Chinese Han population

Human papilloma virus E1-specific T cell immune response is associated with the prognosis of cervical cancer patients with squamous cell carcinoma

Multi-layered Gag-specific immunodominant responses contribute to improved viral control in the CRF01_AE subtype of HIV-1-infected MSM subjects

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