9Y0V

Crystal Structure of human MAIT A-F7 TCR-MR1*04 complex

Summary for 9Y0V

• Entry DOI: 10.2210/pdb9y0v/pdb
• Descriptor: Major histocompatibility complex class I-related protein 1, Beta-2-microglobulin, TCR alpha chain, ... (6 entities in total)
• Functional Keywords: mait tcr, mr1, metabolite presentation, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 8
• Total formula weight: 188376.39

Authors

Letoga, V.,Rossjohn, J.,Awad, W. (deposition date: 2025-08-29, release date: 2026-05-13, Last modification date: 2026-06-03)

Primary citation

Nelson, A.G.,Letoga, V.,Lee, C.Z.Q.,Samer, C.,Li, S.,Meehan, L.J.,McWilliam, H.E.G.,Gherardin, N.A.,Abendroth, A.,Villadangos, J.A.,Slobedman, B.,Corbett, A.J.,McCluskey, J.,Rossjohn, J.,Chen, Z.,Souter, M.N.T.,Awad, W.
Allelic variation alters expression and antigen presentation of MR1 allomorphs.
J.Biol.Chem., 302:111470-111470, 2026

PubMed Abstract: The 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.

PubMed: 42001947
DOI: 10.1016/j.jbc.2026.111470

Experimental method

X-RAY DIFFRACTION (3 Å)