Sop Joel, Beckey Tyler P, Blankson Joel N
Department of Medicine, Johns Hopkins Medicine, Baltimore, MD, United States.
Front Immunol. 2025 May 22;16:1600132. doi: 10.3389/fimmu.2025.1600132. eCollection 2025.
HIV-1 alternative reading frame proteins (ARFPs) have been shown to elicit CD8+ T cell responses, but less is known about the recognition of these proteins by CD4+ T cells. In this study, we analyzed responses of CD8-depleted peripheral blood mononuclear cells from chronic progressors (CPs) on suppressive antiretroviral therapy to ARFP peptide pools derived from HIV Gag, polymerase (Pol), and envelope (Env) proteins. Memory CD4+ T cell responses were detected to Gag ARFP peptide pools in 7 out of 13 CPs and to Env ARFP peptide pools in 2 out of 13 CPs. Individual peptide stimulation identified immunogenic peptides that were predicted to bind to major histocompatibility complex class II (MHC-II) proteins. HIV RNA was detected in culture supernatants from 3 of 6 CPs following stimulation of CD4+ T cells with ARFP peptide pools. These findings demonstrate that ARFP-derived peptides elicit antigen-specific CD4+ T cell responses and may contribute to latency reversal. Our data expand the known HIV immunopeptidome and suggest that ARFPs may serve as potential targets for immune-based interventions.
HIV-1替代阅读框蛋白（ARFPs）已被证明能引发CD8+ T细胞反应，但对于CD4+ T细胞对这些蛋白的识别了解较少。在本研究中，我们分析了接受抑制性抗逆转录病毒治疗的慢性进展者（CPs）中CD8耗竭的外周血单核细胞对源自HIV Gag、聚合酶（Pol）和包膜（Env）蛋白的ARFP肽库的反应。在13名CPs中的7名中检测到对Gag ARFP肽库的记忆性CD4+ T细胞反应，在13名CPs中的2名中检测到对Env ARFP肽库的反应。单个肽刺激鉴定出预测可与主要组织相容性复合体II类（MHC-II）蛋白结合的免疫原性肽。在用ARFP肽库刺激CD4+ T细胞后，在6名CPs中的3名的培养上清液中检测到HIV RNA。这些发现表明，源自ARFP的肽可引发抗原特异性CD4+ T细胞反应，并可能有助于潜伏期逆转。我们的数据扩展了已知的HIV免疫肽组，并表明ARFPs可能作为基于免疫的干预措施的潜在靶点。
