6ZKW

Crystal structure of InhA:01 TCR in complex with HLA-E bound to InhA (53-61)

Summary for 6ZKW

• Entry DOI: 10.2210/pdb6zkw/pdb
• Descriptor: HLA class I histocompatibility antigen, alpha chain E, Beta-2-microglobulin, Enoyl-[acyl-carrier-protein] reductase [NADH], ... (6 entities in total)
• Functional Keywords: t cell receptor, tcr, hla-e, inha, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 93671.85

Authors

Srikannathasan, V.,Karuppiah, V.,Robinson, R.A. (deposition date: 2020-06-30, release date: 2022-01-26, Last modification date: 2024-11-06)

Primary citation

Barber, C.,De Souza, V.A.,Paterson, R.L.,Martin-Urdiroz, M.,Mulakkal, N.C.,Srikannathasan, V.,Connolly, M.,Phillips, G.,Foong-Leong, T.,Pengelly, R.,Karuppiah, V.,Grant, T.,Dembek, M.,Verma, A.,Gibbs-Howe, D.,Blicher, T.H.,Knox, A.,Robinson, R.A.,Cole, D.K.,Leonard, S.
Structure-guided stabilization of pathogen-derived peptide-HLA-E complexes using non-natural amino acids conserves native TCR recognition.
Eur.J.Immunol., 52:618-632, 2022

PubMed Abstract: The nonpolymorphic class Ib molecule, HLA-E, primarily presents peptides from HLA class Ia leader peptides, providing an inhibitory signal to NK cells via CD94/NKG2 interactions. Although peptides of pathogenic origin can also be presented by HLA-E to T cells, the molecular basis underpinning their role in antigen surveillance is largely unknown. Here, we solved a co-complex crystal structure of a TCR with an HLA-E presented peptide (pHLA-E) from bacterial (Mycobacterium tuberculosis) origin, and the first TCR-pHLA-E complex with a noncanonically presented peptide from viral (HIV) origin. The structures provided a molecular foundation to develop a novel method to introduce cysteine traps using non-natural amino acid chemistry that stabilized pHLA-E complexes while maintaining native interface contacts between the TCRs and different pHLA-E complexes. These pHLA-E monomers could be used to isolate pHLA-E-specific T cells, with obvious utility for studying pHLA-E restricted T cells, and for the identification of putative therapeutic TCRs.

PubMed: 35108401
DOI: 10.1002/eji.202149745

Experimental method

X-RAY DIFFRACTION (2.26 Å)