Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, California, United States of America.
Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, California, United States of America.
PLoS One. 2022 Aug 16;17(8):e0268370. doi: 10.1371/journal.pone.0268370. eCollection 2022.
Reagents to monitor T cell responses to the entire HIV genome, based on well characterized epitopes, are missing. Evaluation of HIV-specific T cell responses is of importance to study natural infection, and therapeutic and vaccine interventions. Experimentally derived CD4+ and CD8+ HIV epitopes from the HIV molecular immunology database were developed into Class I and Class II HIV megapools (MPs). We assessed HIV responses in persons with HIV pre antiretroviral therapy (ART) (n = 17) and post-ART (n = 18) and compared these responses to 15 controls without HIV (matched by sex at birth, age, and ethnicity). Using the Activation Induced Marker (AIM) assay, we quantified HIV-specific total CD4+, memory CD4+, circulating T follicular helper, total CD8+ and memory CD8+ T cells. We also compared the Class I and Class II HIV MPs to commercially available HIV gag peptide pools. Overall, HIV Class II MP detected HIV-specific CD4+ T cells in 21/35 (60%) HIV positive samples and 0/15 HIV negative samples. HIV Class I MP detected an HIV-specific CD8+ T cells in 17/35 (48.6%) HIV positive samples and 0/15 HIV negative samples. Our innovative HIV MPs are reflective of the entire HIV genome, and its performance is comparable to other commercially available peptide pools. Here, we detected HIV-specific CD4+ and CD8+ T cell responses in people on and off ART, but not in people without HIV.
用于监测针对整个 HIV 基因组的 T 细胞反应的试剂基于特征明确的表位,但目前仍然缺失。评估 HIV 特异性 T 细胞反应对于研究自然感染以及治疗和疫苗干预至关重要。从 HIV 分子免疫学数据库中实验衍生出的 CD4+和 CD8+HIV 表位被开发成了 I 类和 II 类 HIV 大型混合库(MPs)。我们评估了未接受抗逆转录病毒治疗(ART)(n = 17)和接受 ART 治疗后的 HIV 感染者(n = 18)的 HIV 反应,并将这些反应与 15 名未感染 HIV 的对照者(通过出生时的性别、年龄和种族进行匹配)进行了比较。使用激活诱导标志物(AIM)检测法,我们量化了 HIV 特异性总 CD4+、记忆性 CD4+、循环滤泡辅助性 T 细胞、总 CD8+和记忆性 CD8+T 细胞。我们还将 I 类和 II 类 HIV MPs 与市售的 HIV gag 肽库进行了比较。总体而言,HIV II 类 MPs 在 35 份 HIV 阳性样本中的 21 份(60%)和 15 份 HIV 阴性样本中的 0 份中检测到了 HIV 特异性 CD4+T 细胞。HIV I 类 MPs 在 35 份 HIV 阳性样本中的 17 份(48.6%)和 15 份 HIV 阴性样本中的 0 份中检测到了 HIV 特异性 CD8+T 细胞。我们的创新型 HIV MPs 反映了整个 HIV 基因组,其性能与其他市售的肽库相当。在这里,我们在接受和未接受 ART 治疗的人群中检测到了 HIV 特异性 CD4+和 CD8+T 细胞反应,但在未感染 HIV 的人群中未检测到。