7umg
Crystal structure of human CD8aa-MR1-Ac-6-FP complex
Structural highlights
FunctionHMR1_HUMAN Has antigen presentation function. Involved in the development and expansion of a small population of T-cells expressing an invariant T-cell receptor alpha chain called mucosal-associated invariant T-cells (MAIT). MAIT cells are preferentially located in the gut lamina propria and therefore may be involved in monitoring commensal flora or serve as a distress signal. Expression and MAIT cell recognition seem to be ligand-dependent.[1] Publication Abstract from PubMedMucosal-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 CD8alphaalpha or CD8alphabeta 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 CD8alphaalpha 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-CD8alphaalpha, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8alphaalpha and CD8alphabeta 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 CD8alphaalpha and CD8alphabeta act as functional coreceptors for MAIT and other MR1-reactive T cells. CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells.,Souter MNT, Awad W, Li S, Pediongco TJ, Meehan BS, Meehan LJ, Tian Z, Zhao Z, Wang H, Nelson A, Le Nours J, Khandokar Y, Praveena T, Wubben J, Lin J, Sullivan LC, Lovrecz GO, Mak JYW, Liu L, Kostenko L, Kedzierska K, Corbett AJ, Fairlie DP, Brooks AG, Gherardin NA, Uldrich AP, Chen Z, Rossjohn J, Godfrey DI, McCluskey J, Pellicci DG, Eckle SBG J Exp Med. 2022 Sep 5;219(9):e20210828. doi: 10.1084/jem.20210828. Epub 2022 Aug , 26. PMID:36018322[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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