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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]
Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Engineering Source
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Header DbId: egs
DbLabel: Engineering Source
An: 195088540
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
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Items – Name: Title
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  Data: Allelic variation alters expression and antigen presentation of MR1 allomorphs.
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  Data: <searchLink fieldCode="AR" term="%22Nelson%2C+Adam+G%2E%22">Nelson, Adam G.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Letoga%2C+Victoria%22">Letoga, Victoria</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Lee%2C+Clarice+Z%2E+Q%2E%22">Lee, Clarice Z. Q.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Samer%2C+Carolyn%22">Samer, Carolyn</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Li%2C+Songyi%22">Li, Songyi</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Meehan%2C+Lucy+J%2E%22">Meehan, Lucy J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22McWilliam%2C+Hamish+E%2E+G%2E%22">McWilliam, Hamish E. G.</searchLink><relatesTo>1,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Gherardin%2C+Nicholas+A%2E%22">Gherardin, Nicholas A.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Abendroth%2C+Allison%22">Abendroth, Allison</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Villadangos%2C+Jose+A%2E%22">Villadangos, Jose A.</searchLink><relatesTo>1,4</relatesTo><br /><searchLink fieldCode="AR" term="%22Slobedman%2C+Barry%22">Slobedman, Barry</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Corbett%2C+Alexandra+J%2E%22">Corbett, Alexandra J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22McCluskey%2C+James%22">McCluskey, James</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Rossjohn%2C+Jamie%22">Rossjohn, Jamie</searchLink><relatesTo>2,5</relatesTo><br /><searchLink fieldCode="AR" term="%22Chen%2C+Zhenjun%22">Chen, Zhenjun</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Souter%2C+Michael+N%2E+T%2E%22">Souter, Michael N. T.</searchLink><relatesTo>1</relatesTo><i> michael.souter@unimelb.edu.au</i><br /><searchLink fieldCode="AR" term="%22Awad%2C+Wael%22">Awad, Wael</searchLink><relatesTo>2</relatesTo><i> wael.awad@monash.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. Jun2026, Vol. 302 Issue 6, p1-20. 20p.
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  Data: <searchLink fieldCode="DE" term="%22Genetic+polymorphisms%22">Genetic polymorphisms</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+variation%22">Genetic variation</searchLink><br /><searchLink fieldCode="DE" term="%22Major+histocompatibility+complex%22">Major histocompatibility complex</searchLink><br /><searchLink fieldCode="DE" term="%22Antigen+presentation%22">Antigen presentation</searchLink><br /><searchLink fieldCode="DE" term="%22Herpes+simplex+virus%22">Herpes simplex virus</searchLink><br /><searchLink fieldCode="DE" term="%22Immune+response%22">Immune response</searchLink><br /><searchLink fieldCode="DE" term="%22Lymphocytes%22">Lymphocytes</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+structure%22">Protein structure</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: 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]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.jbc.2026.111470
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      – Code: eng
        Text: English
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        PageCount: 20
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    Subjects:
      – SubjectFull: Genetic polymorphisms
        Type: general
      – SubjectFull: Genetic variation
        Type: general
      – SubjectFull: Major histocompatibility complex
        Type: general
      – SubjectFull: Antigen presentation
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      – SubjectFull: Herpes simplex virus
        Type: general
      – SubjectFull: Immune response
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      – SubjectFull: Lymphocytes
        Type: general
      – SubjectFull: Protein structure
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      – TitleFull: Allelic variation alters expression and antigen presentation of MR1 allomorphs.
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              Text: Jun2026
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