9hi7
Structure of MC.7.G5 T cell receptor in complex with MR1 R9H
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 PubMedINTRODUCTION: The 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/RESULTS: Here 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. DISCUSSION: Our results underscore the importance of in-depth characterization of MR1-reactive TCRs against targets expressing the full repertoire of MR1 allomorphs. Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor.,Suckling RJ, Pamukcu C, Simmons RA, Fonseca D, Grant E, Harrison R, Shaikh SA, Khanolkar RC, Ghadbane H, Creese A, Hock M, Gligoris TG, Lepore M, Karuppiah V, Salio M Front Immunol. 2025 Mar 26;16:1547664. doi: 10.3389/fimmu.2025.1547664. , eCollection 2025. PMID:40207221[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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