DataSheet_1_The Combination of CD8αα and Peptide-MHC-I in a Face-to-Face Mode Promotes Chicken γδT Cells Response.docx

The CD8αα homodimer is crucial to both thymic T cell selection and the antigen recognition of cytotoxic T cells. The CD8-pMHC-I interaction can enhance CTL immunity via stabilizing the TCR-pMHC-I interaction and optimizing the cross-reactivity and Ag sensitivity of CD8+ T cells at various stages of development. To date, only human and mouse CD8-pMHC-I complexes have been determined. Here, we resolved the pBF2*1501 complex and the cCD8αα/pBF2*1501 and cCD8αα/pBF2*0401 complexes in nonmammals for the first time. Remarkably, cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 complex both exhibited two binding modes, including an “antibody-like” mode similar to that of the known mammal CD8/pMHC-I complexes and a “face-to-face” mode that has been observed only in chickens to date. Compared to the “antibody-like” mode, the “face-to-face” binding mode changes the binding orientation of the cCD8αα homodimer to pMHC-I, which might facilitate abundant γδT cells to bind diverse peptides presented by limited BF2 alleles in chicken. Moreover, the forces involving in the interaction of cCD8αα/pBF2*1501 and the cCD8αα/pBF2*0401 are different in this two binding model, which might change the strength of the CD8-pMHC-I interaction, amplifying T cell cross-reactivity in chickens. The coreceptor CD8αα of TCR has evolved two peptide-MHC-I binding patterns in chickens, which might enhance the T cell response to major or emerging pathogens, including chicken-derived pathogens that are relevant to human health, such as high-pathogenicity influenza viruses.

CD8αα同二聚体（CD8αα homodimer）对胸腺T细胞选择与细胞毒性T细胞的抗原识别均至关重要。CD8与肽-主要组织相容性复合体I类（pMHC-I）的相互作用可通过稳定T细胞受体（TCR）-pMHC-I的结合，并优化CD8+ T细胞在不同发育阶段的交叉反应性与抗原敏感性，增强细胞毒性T淋巴细胞（CTL）的免疫应答。迄今为止，仅解析了人类与小鼠的CD8-pMHC-I复合物。本研究首次在非哺乳动物中解析了pBF2*1501复合物，以及cCD8αα/pBF2*1501与cCD8αα/pBF2*0401复合物。值得注意的是，cCD8αα/pBF2*1501与cCD8αα/pBF2*0401复合物均存在两种结合模式：一种是与已知哺乳动物CD8/pMHC-I复合物类似的“抗体样”结合模式，另一种是迄今为止仅在鸡中观测到的“面对面”结合模式。相较于“抗体样”结合模式，“面对面”结合模式改变了cCD8αα同二聚体与pMHC-I的结合取向，这或可帮助鸡体内丰富的γδ T细胞（γδ T cell）结合有限BF2等位基因呈递的多样化肽段。此外，cCD8αα/pBF2*1501与cCD8αα/pBF2*0401相互作用所涉及的分子作用力在两种结合模型中存在差异，这可能改变CD8-pMHC-I相互作用的强度，进而放大鸡体内T细胞的交叉反应性。T细胞的共受体CD8αα在鸡中演化出两种肽-MHC-I结合模式，这或可增强T细胞对主要病原体或新发病原体的免疫应答，包括与人类健康密切相关的鸡源病原体，例如高致病性禽流感病毒。