Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor
IntroductionThe MHC-class-I-related molecule MR1 presents small metabolites of microbial and self-origin to T cells bearing semi-invariant or variant T cell receptors. One such T cell receptor, MC.7.G5, was previously shown to confer broad MR1-restricted reactivity to tumor cells but not normal cell...
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| Language: | English |
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547664/full |
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| author | Richard J. Suckling Cevriye Pamukcu Robert Alan Simmons Daniel Fonseca Emma Grant Rory Harrison Saher A. Shaikh Rahul C. Khanolkar Hemza Ghadbane Andrew Creese Miriam Hock Thomas G. Gligoris Marco Lepore Vijaykumar Karuppiah Mariolina Salio |
| author_facet | Richard J. Suckling Cevriye Pamukcu Robert Alan Simmons Daniel Fonseca Emma Grant Rory Harrison Saher A. Shaikh Rahul C. Khanolkar Hemza Ghadbane Andrew Creese Miriam Hock Thomas G. Gligoris Marco Lepore Vijaykumar Karuppiah Mariolina Salio |
| author_sort | Richard J. Suckling |
| collection | DOAJ |
| description | IntroductionThe MHC-class-I-related molecule MR1 presents small metabolites of microbial and self-origin to T cells bearing semi-invariant or variant T cell receptors. One such T cell receptor, MC.7.G5, was previously shown to confer broad MR1-restricted reactivity to tumor cells but not normal cells, sparking interest in the development of non-MHC-restricted immunotherapy approaches.Methods/ResultsHere we provide cellular, biophysical, and crystallographic evidence that the MC.7.G5 TCR does not have pan-cancer specificity but is restricted to a rare allomorph of MR1, bearing the R9H mutation.DiscussionOur results underscore the importance of in-depth characterization of MR1-reactive TCRs against targets expressing the full repertoire of MR1 allomorphs. |
| format | Article |
| id | doaj-art-e7ba829918e94584bd8926cb3bb1aab1 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-e7ba829918e94584bd8926cb3bb1aab12025-08-20T02:40:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15476641547664Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptorRichard J. SucklingCevriye PamukcuRobert Alan SimmonsDaniel FonsecaEmma GrantRory HarrisonSaher A. ShaikhRahul C. KhanolkarHemza GhadbaneAndrew CreeseMiriam HockThomas G. GligorisMarco LeporeVijaykumar KaruppiahMariolina SalioIntroductionThe MHC-class-I-related molecule MR1 presents small metabolites of microbial and self-origin to T cells bearing semi-invariant or variant T cell receptors. One such T cell receptor, MC.7.G5, was previously shown to confer broad MR1-restricted reactivity to tumor cells but not normal cells, sparking interest in the development of non-MHC-restricted immunotherapy approaches.Methods/ResultsHere we provide cellular, biophysical, and crystallographic evidence that the MC.7.G5 TCR does not have pan-cancer specificity but is restricted to a rare allomorph of MR1, bearing the R9H mutation.DiscussionOur results underscore the importance of in-depth characterization of MR1-reactive TCRs against targets expressing the full repertoire of MR1 allomorphs.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547664/fullMR1cancermetabolitesMAITTCR |
| spellingShingle | Richard J. Suckling Cevriye Pamukcu Robert Alan Simmons Daniel Fonseca Emma Grant Rory Harrison Saher A. Shaikh Rahul C. Khanolkar Hemza Ghadbane Andrew Creese Miriam Hock Thomas G. Gligoris Marco Lepore Vijaykumar Karuppiah Mariolina Salio Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor Frontiers in Immunology MR1 cancer metabolites MAIT TCR |
| title | Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor |
| title_full | Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor |
| title_fullStr | Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor |
| title_full_unstemmed | Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor |
| title_short | Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor |
| title_sort | molecular basis underpinning mr1 allomorph recognition by an mr1 restricted t cell receptor |
| topic | MR1 cancer metabolites MAIT TCR |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1547664/full |
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