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9hi7

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Structure of MC.7.G5 T cell receptor in complex with MR1 R9H

Structural highlights

9hi7 is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.81Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

HMR1_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 PubMed

INTRODUCTION: 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

↑ Miley MJ, Truscott SM, Yu YY, Gilfillan S, Fremont DH, Hansen TH, Lybarger L. Biochemical features of the MHC-related protein 1 consistent with an immunological function. J Immunol. 2003 Jun 15;170(12):6090-8. PMID:12794138
↑ 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. Molecular basis underpinning MR1 allomorph recognition by an MR1-restricted T cell receptor. Front Immunol. 2025 Mar 26;16:1547664. PMID:40207221 doi:10.3389/fimmu.2025.1547664