{"display":true,"structure":{"allele":{"alpha":{"identifier":"uniprot:P01899","locus":"h2-d","match_type":"histo:exact","name":"H2-Db","slug":"h2_db","species_stem":"H2"},"beta":{}},"assemblies":{"1":{"assembly_name":"7umg_1","chains":["A","B","C","D"],"downloaded_at":"2022-11-09T14:30:18.841697"}},"assembly_count":null,"assigned_chains":{"beta2m":{"chains":["B"],"match_type":"histo:assign_chains","score":0.99,"sequence":"MIQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM"},"cd8a":{"chains":["C","D"],"match_type":"histo:assign_chains","score":0.94,"sequence":"MSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGSSWLFQPRGAAASPTFLLYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSNSIMYFSHFVPVFLPAKPTTTPHHHHHH"},"mr1":{"chains":["A"],"match_type":"histo:assign_chains","score":1.0,"sequence":"MRTHSLRYFRLGVSDPIHGVPEFISVGYVDSHPITTYDSVTRQKEPRAPWMAENLAPDHWERYTQLLRGWQQMFKVELKRLQRHYNHSGSHTYQRMIGCELLEDGSTTGFLQYAYDGQDFLIFNKDTLSWLAVDNVAHTIKQAWEANQHELLYQKNWLEEECIAWLKRFLEYGKDTLQRTEPPLVRVNRKETFPGVTALFCKAHGFYPPEIYMTWMKNGEEIVQEIDYGDILPSGDGTYQAWASIELDPQSSNLYSCHVEHSGVHMVLQVP"}},"chronology":{"deposition_date":"2022-04-06","deposition_year":2022,"release_date":"2022-08-03","release_year":2022,"revision_date":"2022-09-14","revision_year":2022},"class":"class_i","classical":false,"complex_type":"mr1_with_cd8a","components":["mr1","beta2m","cd8a"],"experimental_method":"X-ray diffraction","facets":{},"ligands":[],"locus":"h2-d","manually_edited":{},"missing_residues":[],"page_title":"7UMG | Non-classical MHC Class I molecule MR1 with CD8a","pdb_code":"7umg","pdb_title":"Crystal structure of human cd8aa-MR1-ac-6-fp complex","peptide":{"actual_sequence":null,"epitope_info":{},"features":[],"full_sequence":null,"gap_info":{},"gapped_sequence":null,"length":{"numeric":null,"text":null},"unnatural_amino_acids":[]},"publication":{"abstract":"Mucosal-associated invariant T (MAIT) cells detect microbial infection via recognition of riboflavin-based antigens presented by the major histocompatibility complex class I (MHC-I)-related protein 1 (MR1). Most MAIT cells in human peripheral blood express CD8\u03b1\u03b1 or CD8\u03b1\u03b2 coreceptors, and the binding site for CD8 on MHC-I molecules is relatively conserved in MR1. Yet, there is no direct evidence of CD8 interacting with MR1 or the functional consequences thereof. Similarly, the role of CD8\u03b1\u03b1 in lymphocyte function remains ill-defined. Here, using newly developed MR1 tetramers, mutated at the CD8 binding site, and by determining the crystal structure of MR1-CD8\u03b1\u03b1, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8\u03b1\u03b1 and CD8\u03b1\u03b2 enhanced MR1 binding and cytokine production by MAIT cells. Moreover, the CD8-MR1 interaction was critical for the recognition of folate-derived antigens by other MR1-reactive T cells. Together, our findings suggest that both CD8\u03b1\u03b1 and CD8\u03b1\u03b2 act as functional coreceptors for MAIT and other MR1-reactive T cells.","bibjson":{"author":[{"initials":"MNT","lastname":"Souter","name":"Souter MNT"},{"initials":"W","lastname":"Awad","name":"Awad W"},{"initials":"S","lastname":"Li","name":"Li S"},{"initials":"TJ","lastname":"Pediongco","name":"Pediongco TJ"},{"initials":"BS","lastname":"Meehan","name":"Meehan BS"},{"initials":"LJ","lastname":"Meehan","name":"Meehan LJ"},{"initials":"Z","lastname":"Tian","name":"Tian Z"},{"initials":"Z","lastname":"Zhao","name":"Zhao Z"},{"initials":"H","lastname":"Wang","name":"Wang H"},{"initials":"A","lastname":"Nelson","name":"Nelson A"},{"initials":"J","lastname":"Le Nours","name":"Le Nours J"},{"initials":"Y","lastname":"Khandokar","name":"Khandokar Y"},{"initials":"T","lastname":"Praveena","name":"Praveena T"},{"initials":"J","lastname":"Wubben","name":"Wubben J"},{"initials":"J","lastname":"Lin","name":"Lin J"},{"initials":"LC","lastname":"Sullivan","name":"Sullivan LC"},{"initials":"GO","lastname":"Lovrecz","name":"Lovrecz GO"},{"initials":"JYW","lastname":"Mak","name":"Mak JYW"},{"initials":"L","lastname":"Liu","name":"Liu L"},{"initials":"L","lastname":"Kostenko","name":"Kostenko L"},{"initials":"K","lastname":"Kedzierska","name":"Kedzierska K"},{"initials":"AJ","lastname":"Corbett","name":"Corbett AJ"},{"initials":"DP","lastname":"Fairlie","name":"Fairlie DP"},{"initials":"AG","lastname":"Brooks","name":"Brooks AG"},{"initials":"NA","lastname":"Gherardin","name":"Gherardin NA"},{"initials":"AP","lastname":"Uldrich","name":"Uldrich AP"},{"initials":"Z","lastname":"Chen","name":"Chen Z"},{"initials":"J","lastname":"Rossjohn","name":"Rossjohn J"},{"initials":"DI","lastname":"Godfrey","name":"Godfrey DI"},{"initials":"J","lastname":"McCluskey","name":"McCluskey J"},{"initials":"DG","lastname":"Pellicci","name":"Pellicci DG"},{"initials":"SBG","lastname":"Eckle","name":"Eckle SBG"}],"identifier":[{"id":"10.1084/jem.20210828","type":"doi"},{"id":"36018322","type":"pubmed"}],"issue":["9"],"journal":{"iso_abbreviation":"J Exp Med","name":""},"pages":[null],"title":"CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells.","type":"article","url":"https://rupress.org/jem/article/219/9/e20210828/213423/CD8-coreceptor-engagement-of-MR1-enhances-antigen","volume":["219"],"year":[2022]},"in_pmc":"N","in_pmce":"N","open_access":"N"},"resolution":"2.40","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/7umg"},"rcsb":{"url":"https://www.rcsb.org/structure/7umg"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"Non-classical MHC Class I molecule MR1 with CD8a at 2.40Å resolution","unique_chain_count":3}}