aINSERM UMR S 945, Infections and Immunity, Université Pierre et Marie Curie-Paris6, Hôpital Pitié-Salpêtrière, Paris, France bInstitute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, Wales, UK cInstitut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France. *Anna Lissina and Solène Fastenackels contributed equally to this writing of this work. †Current address: Centro de Investigacion en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City, Mexico.
AIDS. 2014 Feb 20;28(4):477-86. doi: 10.1097/QAD.0000000000000175.
Although it is established that CD8 T-cell immunity is critical for the control of HIV replication in vivo, the key factors that determine antiviral efficacy are yet to be fully elucidated. Antigen-sensitivity and T-cell receptor (TCR) avidity have been identified as potential determinants of CD8⁺ T-cell efficacy. However, there is no general consensus in this regard because the relationship between these parameters and the control of HIV infection has been established primarily in the context of immunodominant CD8⁺ T-cell responses against the Gag₂₆₃₋₂₇₂ KK10 epitope restricted by human leukocyte antigen (HLA)-B27.
To investigate the relationship between antigen-sensitivity, TCR avidity and HIV-suppressive capacity in vitro across epitope specificities and HLA class I restriction elements, we used a variety of techniques to study CD8⁺ T-cell clones specific for Nef₇₃₋₈₂ QK10 and Gag₂₀₋₂₉ RY10, both restricted by HLA-A3, alongside CD8⁺ T-cell clones specific for Gag₂₆₃₋₂₇₂ KK10.
For each targeted epitope, the linked parameters of antigen-sensitivity and TCR avidity correlated directly with antiviral efficacy. However, marked differences in HIV-suppressive capacity were observed between epitope specificities, HLA class I restriction elements and viral isolates.
Collectively, these data emphasize the central role of the TCR as a determinant of CD8⁺ T-cell efficacy and demonstrate that the complexities of antigen recognition across epitope and HLA class I boundaries can confound simple relationships between TCR engagement and HIV suppression.
虽然已经确定 CD8 T 细胞免疫对于控制体内 HIV 复制至关重要，但决定抗病毒疗效的关键因素尚未完全阐明。抗原敏感性和 T 细胞受体（TCR）亲合力已被确定为 CD8+T 细胞疗效的潜在决定因素。然而，由于这些参数与 HIV 感染控制之间的关系主要是在针对 Gag₂₆₃₋₂₇₂ KK10 表位的免疫优势 CD8+T 细胞反应的背景下确定的，这些反应受人类白细胞抗原（HLA）-B27 限制，因此在这方面没有普遍共识。
为了研究抗原敏感性、TCR 亲合力与体外 HIV 抑制能力之间的关系，跨越表位特异性和 HLA Ⅰ类限制元件，我们使用多种技术研究了针对 Nef₇₃₋₈₂ QK10 和 Gag₂₀₋₂₉ RY10 的 CD8+T 细胞克隆，这两种克隆均受 HLA-A3 限制，同时还研究了针对 Gag₂₆₃₋₂₇₂ KK10 的 CD8+T 细胞克隆。
对于每个靶向表位，抗原敏感性和 TCR 亲合力的相关参数与抗病毒疗效直接相关。然而，在表位特异性、HLA Ⅰ类限制元件和病毒分离株之间，观察到 HIV 抑制能力的显著差异。
总的来说，这些数据强调了 TCR 作为 CD8+T 细胞疗效决定因素的核心作用，并表明抗原识别的复杂性跨越表位和 HLA Ⅰ类边界可能会使 TCR 结合与 HIV 抑制之间的简单关系复杂化。
