6w9u

From Proteopedia

Structure of human MAIT A-F7 TCR in complex with patient MR1-R9H-Ac-6-FP

Structural highlights

6w9u 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 1.89Å
Ligands:	, ,
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

The role unconventional T cells play in protective immunity in humans is unclear. Mucosal-associated invariant T (MAIT) cells are an unconventional T cell subset restricted to the antigen-presenting molecule MR1. Here, we report the discovery of a patient homozygous for a rare Arg31His (R9H in the mature protein) mutation in MR1 who has a history of difficult-to-treat viral and bacterial infections. MR1(R9H) was unable to present the potent microbially derived MAIT cell stimulatory ligand. The MR1(R9H) crystal structure revealed that the stimulatory ligand cannot bind due to the mutation lying within, and causing structural perturbation to, the ligand-binding domain of MR1. While MR1(R9H) could bind and be up-regulated by a MAIT cell inhibitory ligand, the patient lacked circulating MAIT cells. This shows the importance of the stimulatory ligand for MAIT cell selection in humans. The patient had an expanded gammadelta T cell population, indicating a compensatory interplay between these unconventional T cell subsets.

Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1.,Howson LJ, Awad W, von Borstel A, Lim HJ, McWilliam HEG, Sandoval-Romero ML, Majumdar S, Hamzeh AR, Andrews TD, McDermott DH, Murphy PM, Le Nours J, Mak JYW, Liu L, Fairlie DP, McCluskey J, Villadangos JA, Cook MC, Turner SJ, Davey MS, Ojaimi S, Rossjohn J Sci Immunol. 2020 Jul 24;5(49). pii: 5/49/eabc9492. doi:, 10.1126/sciimmunol.abc9492. PMID:32709702^[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
↑ Howson LJ, Awad W, von Borstel A, Lim HJ, McWilliam HEG, Sandoval-Romero ML, Majumdar S, Hamzeh AR, Andrews TD, McDermott DH, Murphy PM, Le Nours J, Mak JYW, Liu L, Fairlie DP, McCluskey J, Villadangos JA, Cook MC, Turner SJ, Davey MS, Ojaimi S, Rossjohn J. Absence of mucosal-associated invariant T cells in a person with a homozygous point mutation in MR1. Sci Immunol. 2020 Jul 24;5(49):eabc9492. PMID:32709702 doi:10.1126/sciimmunol.abc9492