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Allelic variation alters expression and antigen presentation of MR1 allomorphs.

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Title: Allelic variation alters expression and antigen presentation of MR1 allomorphs.
Authors: Nelson, Adam G.1, Letoga, Victoria2, Lee, Clarice Z. Q.1, Samer, Carolyn3, Li, Songyi1, Meehan, Lucy J.1, McWilliam, Hamish E. G.1,4, Gherardin, Nicholas A.1, Abendroth, Allison3, Villadangos, Jose A.1,4, Slobedman, Barry3, Corbett, Alexandra J.1, McCluskey, James1, Rossjohn, Jamie2,5, Chen, Zhenjun1, Souter, Michael N. T.1 michael.souter@unimelb.edu.au, Awad, Wael2 wael.awad@monash.edu
Source: Journal of Biological Chemistry. Jun2026, Vol. 302 Issue 6, p1-20. 20p.
Subjects: Genetic polymorphisms, Genetic variation, Major histocompatibility complex, Antigen presentation, Herpes simplex virus, Immune response, Lymphocytes, Protein structure
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 threedimensional 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 stabilizing 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 was 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. [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
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 threedimensional 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 stabilizing 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 was 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. [ABSTRACT FROM AUTHOR]
ISSN:00219258
DOI:10.1016/j.jbc.2026.111470