Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Key Laboratory for Insect-Pollinator Biology of the Ministry of Agriculture, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, China.
Front Immunol. 2020 Nov 23;11:605085. doi: 10.3389/fimmu.2020.605085. eCollection 2020.
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 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 pBF21501 complex and the cCD8αα/pBF21501 and cCD8αα/pBF20401 complexes in nonmammals for the first time. Remarkably, cCD8αα/pBF21501 and the cCD8αα/pBF20401 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/pBF21501 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 同源二聚体对于胸腺 T 细胞选择和细胞毒性 T 细胞的抗原识别都至关重要。CD8-pMHC-I 相互作用可以增强 CTL 免疫，稳定 TCR-pMHC-I 相互作用，并优化 CD8 T 细胞在不同发育阶段的交叉反应性和 Ag 敏感性。迄今为止，仅确定了人源和鼠源 CD8-pMHC-I 复合物。在这里，我们首次解析了非哺乳动物中的 pBF21501 复合物以及 cCD8αα/pBF21501 和 cCD8αα/pBF20401 复合物。值得注意的是，cCD8αα/pBF21501 和 cCD8αα/pBF20401 复合物均表现出两种结合模式，包括类似于已知哺乳动物 CD8/pMHC-I 复合物的“抗体样”模式和迄今为止仅在鸡中观察到的“面对面”模式。与“抗体样”模式相比，“面对面”结合模式改变了 cCD8αα 同源二聚体与 pMHC-I 的结合方向，这可能有利于丰富的 γδT 细胞结合鸡中有限 BF2 等位基因呈递的多种肽。此外，cCD8αα/pBF21501 和 cCD8αα/pBF2*0401 相互作用涉及的力在这两种结合模型中是不同的，这可能改变 CD8-pMHC-I 相互作用的强度，从而放大鸡中 T 细胞的交叉反应性。TCR 的共受体 CD8αα 在鸡中进化出两种肽-MHC-I 结合模式，这可能增强了鸡对主要或新兴病原体的 T 细胞反应，包括与人类健康相关的鸡源性病原体，如高致病性流感病毒。
