Key Points Overlapping IAV peptides are recognized by completely distinct CD8 T cell populations. Distinct T cell reactivities are reflected in TCR use, function, and naive repertoire. The single amino acid peptide extension drives distinct peptide conformations within H-2Db. Visual Abstract The presentation of pathogen-derived peptides on MHC class I molecules is essential for the initiation of adaptive CD8+ T cell immunity, which in turn is critical for effective control of many significant human infections. The identification of immunogenic pathogen-derived epitopes and a detailed understanding of how they are recognized by TCRs is essential for the design of effective T cell–based vaccines. In this study, we have characterized the T cell recognition and immune responses in mice to two naturally presented influenza A virus–derived peptides previously identified from virally infected cells via mass spectrometry. These neuraminidase-derived peptides, NA181–190 (SGPDNGAVAV) and NA181–191 (SGPDNGAVAVL), are completely overlapping with the exception of a 1 aa extension at the C terminus of the longer peptide. This minor peptidic difference results in the induction of two completely independent and non–cross-reactive T cell populations that show distinct functional characteristics after influenza A virus infection of B6 mice. We show that the unique TCR reactivity to the overlapping peptides is present in the naive repertoire prior to immune expansion in B6 mice. Moreover, we provide a structural explanation underlying the distinct CD8+ T cell reactivities, which reinforces the concept that peptide length is a key determinant of Ag specificity in CD8+ T cell responses.

中文翻译：

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重叠肽在甲型流感病毒感染后引发不同的 CD8+ T 细胞反应

关键点重叠 IAV 肽被完全不同的 CD8 T 细胞群识别。不同的 T 细胞反应性反映在 TCR 的使用、功能和幼稚的曲目中。单氨基酸肽延伸驱动 H-2Db 内不同的肽构象。视觉摘要 在 MHC I 类分子上呈递病原体衍生肽对于启动适应性 CD8+ T 细胞免疫至关重要，而这反过来对于有效控制许多重要的人类感染至关重要。鉴定免疫原性病原体衍生表位并详细了解它们如何被 TCR 识别对于设计有效的基于 T 细胞的疫苗至关重要。在这项研究中，我们已经表征了小鼠对两种天然呈递的甲型流感病毒衍生肽的 T 细胞识别和免疫反应，这些肽之前通过质谱法从病毒感染的细胞中鉴定出来。这些神经氨酸酶衍生肽，NA181-190 (SGPDNGAVAV) 和 NA181-191 (SGPDDNGAVAVL)，除了较长肽的 C 末端有 1 个氨基酸延伸外，完全重叠。这种微小的肽差异导致在 B6 小鼠感染甲型流感病毒后诱导出两种完全独立且无交叉反应的 T 细胞群，这些 T 细胞群显示出不同的功能特征。我们表明，在 B6 小鼠的免疫扩增之前，原始组中存在对重叠肽的独特 TCR 反应性。而且，