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The CD8-pMHC-I interaction can enhance CTL immunity <i>via</i> stabilizing the TCR-pMHC-I interaction and optimizing the cross-reactivity and Ag sensitivity of CD8<sup>+</sup> 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 cCD8\u03b1\u03b1/pBF2*1501 and cCD8\u03b1\u03b1/pBF2*0401 complexes in nonmammals for the first time. Remarkably, cCD8\u03b1\u03b1/pBF2*1501 and the cCD8\u03b1\u03b1/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 cCD8\u03b1\u03b1 homodimer to pMHC-I, which might facilitate abundant \u03b3\u03b4T cells to bind diverse peptides presented by limited BF2 alleles in chicken. Moreover, the forces involving in the interaction of cCD8\u03b1\u03b1/pBF2*1501 and the cCD8\u03b1\u03b1/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 CD8\u03b1\u03b1 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.","bibjson":{"author":[{"initials":"Y","lastname":"Liu","name":"Liu Y"},{"initials":"R","lastname":"Chen","name":"Chen R"},{"initials":"R","lastname":"Liang","name":"Liang R"},{"initials":"B","lastname":"Sun","name":"Sun B"},{"initials":"Y","lastname":"Wu","name":"Wu Y"},{"initials":"L","lastname":"Zhang","name":"Zhang L"},{"initials":"J","lastname":"Kaufman","name":"Kaufman J"},{"initials":"C","lastname":"Xia","name":"Xia C"}],"identifier":[{"id":"10.3389/fimmu.2020.605085","type":"doi"},{"id":"33329601","type":"pubmed"}],"issue":[null],"journal":{"iso_abbreviation":"Front Immunol","name":""},"pages":["605085"],"title":"The Combination of CD8\ufffd\ufffd\ufffd\ufffd and Peptide-MHC-I in a Face-to-Face Mode Promotes Chicken \ufffd\ufffd\ufffd\ufffdT Cells Response.","type":"article","url":"https://www.frontiersin.org/articles/10.3389/fimmu.2020.605085/full","volume":["11"],"year":[2020]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.80","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6lhg"},"rcsb":{"url":"https://www.rcsb.org/structure/6lhg"}},"species":{"common_name":"Chicken","match_type":"histo:assign_species","scientific_name":"Gallus gallus","slug":"gallus_gallus"},"tcr":null,"title":"Gaga-BF2*004:01 binding \"IDWFDGKE\" with CD8a at 2.80&#8491; resolution","unique_chain_count":4}}