5D7I

Structure of human MR1-Ac-6-FP in complex with human MAIT M33.64 TCR

Summary for 5D7I

• Entry DOI: 10.2210/pdb5d7i/pdb
• Related: 5D5M 5D7J 5D7K 5D7L
• Descriptor: Major histocompatibility complex class I-related gene protein, Beta-2-microglobulin, M33.64 TCR Alpha Chain, ... (8 entities in total)
• Functional Keywords: antigen, receptor, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Single-pass membrane protein; Extracellular side. Isoform 4: Secreted. Isoform 3: Cell membrane ; Single-pass type I membrane protein : Q95460; Secreted : P61769
• Total number of polymer chains: 8
• Total formula weight: 188730.71

Authors

Keller, A.N.,Woolley, R.E.,Rossjohn, J. (deposition date: 2015-08-14, release date: 2016-01-27, Last modification date: 2024-11-20)

Primary citation

Gherardin, N.A.,Keller, A.N.,Woolley, R.E.,Le Nours, J.,Ritchie, D.S.,Neeson, P.J.,Birkinshaw, R.W.,Eckle, S.B.,Waddington, J.N.,Liu, L.,Fairlie, D.P.,Uldrich, A.P.,Pellicci, D.G.,McCluskey, J.,Godfrey, D.I.,Rossjohn, J.
Diversity of T Cells Restricted by the MHC Class I-Related Molecule MR1 Facilitates Differential Antigen Recognition.
Immunity, 44:32-45, 2016

PubMed Abstract: A characteristic of mucosal-associated invariant T (MAIT) cells is the expression of TRAV1-2(+) T cell receptors (TCRs) that are activated by riboflavin metabolite-based antigens (Ag) presented by the MHC-I related molecule, MR1. Whether the MR1-restricted T cell repertoire and associated Ag responsiveness extends beyond these cells remains unclear. Here, we describe MR1 autoreactivity and folate-derivative reactivity in a discrete subset of TRAV1-2(+) MAIT cells. This recognition was attributable to CDR3β loop-mediated effects within a consensus TRAV1-2(+) TCR-MR1-Ag footprint. Furthermore, we have demonstrated differential folate- and riboflavin-derivative reactivity by a diverse population of "atypical" TRAV1-2(-) MR1-restricted T cells. We have shown that TRAV1-2(-) T cells are phenotypically heterogeneous and largely distinct from TRAV1-2(+) MAIT cells. A TRAV1-2(-) TCR docks more centrally on MR1, thereby adopting a markedly different molecular footprint to the TRAV1-2(+) TCR. Accordingly, diversity within the MR1-restricted T cell repertoire leads to differing MR1-restricted Ag specificity.

PubMed: 26795251
DOI: 10.1016/j.immuni.2015.12.005

Experimental method

X-RAY DIFFRACTION (2 Å)