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首页> 外文期刊>Vaccine >Heteroclitic peptides enhance human immunodeficiency virus-specific CD8(+) T cell responses
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Heteroclitic peptides enhance human immunodeficiency virus-specific CD8(+) T cell responses

机译：异气候肽增强人类免疫缺陷病毒特异性CD8（+）T细胞反应

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The inability of human immunodeficiency virus (HIV)-specific CD8+ T cells to durably control HIV replication due to HIV escape mutations and CD8+ T cell dysfunction is a key factor in disease progression. A few HIV-infected individuals termed elite controllers (EC) maintain polyfunctional HIV-specific CD8+ T cells, minimal HIV replication and normal CD4+ T lymphocyte numbers. Thus, therapeutic intervention to sustain or restore CD8+ T cell responses similar to those persisting in EC could relieve terminal dependence on antiretrovirals. Vaccination with HIV peptides is one approach to achieve this and our objective in this study was to determine whether certain HIV peptide variants display antigenic superiority over the reference peptides normally included in vaccines. Eight peptide sets were generated, each with a reference peptide and six variants harboring conservative or semi-conservative amino acid substitutions at positions predicted to affect T cell receptor interactions without affecting human class I histocompatibililty-linked antigen (HLA) binding. Recognition across peptide sets was tested with >80 HIV-infected individuals bearing the appropriate HLA alleles. While reference peptides were often the most antigenic, cross-reactivity with variants was common and in many cases, peptide variants were superior at stimulating interferon-γ production or selectively enhanced interleukin-2 production. Although such heteroclitic activity was not generalized for all individuals bearing the HLA class I allele involved, these data suggest that heteroclitic peptide variants could improve the efficacy of therapeutic peptide vaccines in HIV infection.
机译：由于HIV逃逸突变和CD8 + T细胞功能障碍，人类免疫缺陷病毒（HIV）特异的CD8 + T细胞无法持久地控制HIV复制是疾病进展的关键因素。少数被称为精英控制者（EC）的被HIV感染的个体维持着多功能的HIV特异性CD8 + T细胞，最小的HIV复制和正常的CD4 + T淋巴细胞数量。因此，维持或恢复与EC中持续存在的CD8 + T细胞反应相似的治疗干预措施可以缓解对抗逆转录病毒药物的终末依赖性。用HIV肽进行疫苗接种是实现这一目标的一种方法，我们在本研究中的目标是确定某些HIV肽变体相对于疫苗中通常包含的参考肽是否显示出抗原优势。产生了八组肽，每组具有参考肽和六个变异体，这些变异体在预计会影响T细胞受体相互作用而不影响人I类组织相容性连接抗原（HLA）结合的位置上具有保守或半保守氨基酸取代。对超过80个带有适当HLA等位基因的HIV感染者进行了跨多肽集的识别测试。虽然参考肽通常是最具抗原性的，但与变体的交叉反应是常见的，并且在许多情况下，肽变体在刺激干扰素-γ产生或选择性增强白介素-2产生方面表现优异。尽管未对涉及HLA I类等位基因的所有个体都推广这种异专一性的活动，但这些数据表明异专一肽变体可以提高治疗性肽疫苗在HIV感染中的功效。

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