CD8 coreceptor engagement of MR1 enhances antigen responsiveness by human MAIT and other MR1-reactive T cells

• DOI: 10.1084/jem.20210828
• Publication Date: 2022-08-26T13:53:59Z
• Authors: Michael N.T. Souter; Wael Awad; Shihan Li; Troi J. Pediongco; Bronwyn S. Meehan; Lucy J. Meehan; Zehua Tian; Zhe Zhao; Huimeng Wang; Adam Nelson; Jérôme Le Nours; Yogesh Khandokar; T. Praveena; Jacinta Wubben; Jie Lin; Lucy C. Sullivan; George O. Lovrecz; Jeffrey Y.W. Mak; Ligong Liu; Lyudmila Kostenko; Katherine Kedzierska; Alexandra J. Corbett; David P. Fairlie; Andrew G. Brooks; Nicholas A. Ghera...; Adam P. Uldrich; Zhenjun Chen; Jamie Rossjohn; Dale I. Godfrey; James McCluskey; Daniel G. Pellicci; Sidonia B.G. Eckle
• Keywords: 570; CD8 Antigens; Receptors, Antigen, T-Cell, alpha-beta; Histocompatibility Antigens Class I; 610; CD8-Positive T-Lymphocytes; Article; Mucosal-Associated Invariant T Cells; Minor Histocompatibility Antigens; 03 medical and health sciences; 0302 clinical medicine; Humans; Antigens

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 in human peripheral blood express CD8αα or CD8αβ coreceptors, and binding site for CD8 on MHC-I molecules is relatively conserved MR1. Yet, there no direct evidence interacting with MR1 functional consequences thereof. Similarly, role lymphocyte function remains ill-defined. Here, using newly developed tetramers, mutated at site, determining crystal structure MR1–CD8αα, we show that engaged MR1, analogous to how it engages molecules. enhanced cytokine production cells. Moreover, CD8–MR1 interaction was critical folate-derived other MR1-reactive Together, our findings suggest both act as coreceptors