5W1W

Structure of the HLA-E-VMAPRTLVL/GF4 TCR complex

Summary for 5W1W

• Entry DOI: 10.2210/pdb5w1w/pdb
• Related: 5w1v
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, leader peptide of HLA class I histocompatibility antigen, A alpha chain, ... (5 entities in total)
• Functional Keywords: t-cell receptor, tcr, hla-e, cmv, pmhc-tcr complex, immune system
• Biological source: Homo sapiens (Human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P13747; Secreted . Note=(Microbial infection) In the presence of M: P61769
• Total number of polymer chains: 20
• Total formula weight: 381038.03

Authors

Gras, S.,Walpole, N.,Farenc, C.,Rossjohn, J. (deposition date: 2017-06-05, release date: 2017-10-04, Last modification date: 2024-11-20)

Primary citation

Sullivan, L.C.,Walpole, N.G.,Farenc, C.,Pietra, G.,Sum, M.J.W.,Clements, C.S.,Lee, E.J.,Beddoe, T.,Falco, M.,Mingari, M.C.,Moretta, L.,Gras, S.,Rossjohn, J.,Brooks, A.G.
A conserved energetic footprint underpins recognition of human leukocyte antigen-E by two distinct alpha beta T cell receptors.
J. Biol. Chem., 292:21149-21158, 2017

PubMed Abstract: αβ T cell receptors (TCRs) interact with peptides bound to the polymorphic major histocompatibility complex class Ia (MHC-Ia) and class II (MHC-II) molecules as well as the essentially monomorphic MHC class Ib (MHC-Ib) molecules. Although there is a large amount of information on how TCRs engage with MHC-Ia and MHC-II, our understanding of TCR/MHC-Ib interactions is very limited. Infection with cytomegalovirus (CMV) can elicit a CD8 T cell response restricted by the human MHC-Ib molecule human leukocyte antigen (HLA)-E and specific for an epitope from UL40 (VMAPRTLIL), which is characterized by biased TRBV14 gene usage. Here we describe an HLA-E-restricted CD8 T cell able to recognize an allotypic variant of the UL40 peptide with a modification at position 8 (P8) of the peptide (VMAPRTLVL) that uses the TRBV9 gene segment. We report the structures of a TRBV9 TCR in complex with the HLA-E molecule presenting the two peptides. Our data revealed that the TRBV9 TCR adopts a different docking mode and molecular footprint atop HLA-E when compared with the TRBV14 TCR-HLA-E ternary complex. Additionally, despite their differing V gene segment usage and different docking mechanisms, mutational analyses showed that the TCRs shared a conserved energetic footprint on the HLA-E molecule, focused around the peptide-binding groove. Hence, we provide new insights into how monomorphic MHC molecules interact with T cells.

PubMed: 28972140
DOI: 10.1074/jbc.M117.807719

Experimental method

X-RAY DIFFRACTION (3.1 Å)