7UMG

Crystal structure of human CD8aa-MR1-Ac-6-FP complex

Summary for 7UMG

• Entry DOI: 10.2210/pdb7umg/pdb
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, T-cell surface glycoprotein CD8 alpha chain, ... (7 entities in total)
• Functional Keywords: cd8 coreceptor, mr1, metabolite presentation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 72795.20

Authors

Awad, W.,Rossjohn, J. (deposition date: 2022-04-06, release date: 2022-08-03, Last modification date: 2024-10-30)

Primary citation

Souter, M.N.T.,Awad, W.,Li, S.,Pediongco, T.J.,Meehan, B.S.,Meehan, L.J.,Tian, Z.,Zhao, Z.,Wang, H.,Nelson, A.,Le Nours, J.,Khandokar, Y.,Praveena, T.,Wubben, J.,Lin, J.,Sullivan, L.C.,Lovrecz, G.O.,Mak, J.Y.W.,Liu, L.,Kostenko, L.,Kedzierska, K.,Corbett, A.J.,Fairlie, D.P.,Brooks, A.G.,Gherardin, N.A.,Uldrich, A.P.,Chen, Z.,Rossjohn, J.,Godfrey, D.I.,McCluskey, J.,Pellicci, D.G.,Eckle, S.B.G.
CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells.
J.Exp.Med., 219:-, 2022

PubMed 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 CD8αα or CD8αβ 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 CD8αα 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-CD8αα, we show that CD8 engaged MR1, analogous to how it engages MHC-I molecules. CD8αα and CD8αβ 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 CD8αα and CD8αβ act as functional coreceptors for MAIT and other MR1-reactive T cells.

PubMed: 36018322
DOI: 10.1084/jem.20210828

Experimental method

X-RAY DIFFRACTION (2.4 Å)