9y0v
Crystal Structure of human MAIT A-F7 TCR-MR1*04 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 PubMedThe major histocompatibility complex (MHC) class I-related protein 1 (MR1) presents vitamin B- derived metabolites to mucosal-associated invariant T (MAIT) and other T cells. There is limited polymorphism of MR1, the functional impact of which is not understood. We examined the impact of allelic variation of MR1 on the expression, structure and function of the known MR1 allomorphs. The expression and function of MR1*02, MR1*03 and MR1*06 were similar to the canonical MR1*01. Crystal structures of four MR1 allomorphs show that their polymorphisms do not impact the three-dimensional fold of MR1. Despite the binding of 5-OP-RU to MR1*05 and its cell surface upregulation, this allomorph was severely impaired in its ability to activate primary MAIT cells. This phenotype was controlled by two (His90Gln and Glu52Gly) of its three polymorphisms, which led to the loss of structurally stabilising interactions. When cells expressing the MR1 allomorphs were infected with herpes simplex virus type 1 (HSV-1), the nascent expression of all allomorphs was severely impaired, but surface expression of MR1*04:01 and MR1*04:02 were relatively less impacted. Hence, MR1 allelic variation alters the expression and function of the MR1*04 and MR1*05 allomorphs, with implications for MAIT cell and diverse MR1-reactive T cell immunity. Allelic variation alters expression and antigen presentation of MR1 allomorphs.,Nelson AG, Letoga V, Lee CZQ, Samer C, Li S, Meehan LJ, McWilliam HEG, Gherardin NA, Abendroth A, Villadangos JA, Slobedman B, Corbett AJ, McCluskey J, Rossjohn J, Chen Z, Souter MNT, Awad W J Biol Chem. 2026 Apr 17:111470. doi: 10.1016/j.jbc.2026.111470. PMID:42001947[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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