6D7G

Structure of 5F3 TCR in complex with HLA-A2/MART-1

Summary for 6D7G

• Entry DOI: 10.2210/pdb6d7g/pdb
• Descriptor: MART1 PEPTIDE-BETA-2-MICROGLOBULIN-HLA-A*02 CHIMERA, TRA@ protein, T-CELL RECEPTOR GAMMA VARIABLE 8,T-CELL RECEPTOR GAMMA-2 CHAIN C REGION, ... (5 entities in total)
• Functional Keywords: tcr, mhc, peptide recognition, complex, immune system
• Biological source: Homo sapiens (HUMAN); More
• Total number of polymer chains: 3
• Total formula weight: 103229.25

Authors

Roy, S.,Adams, E.J. (deposition date: 2018-04-24, release date: 2019-01-23, Last modification date: 2024-10-23)

Primary citation

Benveniste, P.M.,Roy, S.,Nakatsugawa, M.,Chen, E.L.Y.,Nguyen, L.,Millar, D.G.,Ohashi, P.S.,Hirano, N.,Adams, E.J.,Zuniga-Pflucker, J.C.
Generation and molecular recognition of melanoma-associated antigen-specific human gamma delta T cells.
Sci Immunol, 3:-, 2018

PubMed Abstract: Antigen recognition by T cells bearing αβ T cell receptors (TCRs) is restricted by major histocompatibility complex (MHC). However, how antigens are recognized by T cells bearing γδ TCRs remains unclear. Although γδ T cells can recognize nonclassical MHC, it is generally thought that recognition of antigens is not MHC restricted. Here, we took advantage of an in vitro system to generate antigen-specific human T cells and show that melanoma-associated antigens, MART-1 and gp100, can be recognized by γδ T cells in an MHC-restricted fashion. Cloning and transferring of MART-1-specific γδ TCRs restored the specific recognition of the initial antigen MHC/peptide reactivity and conferred antigen-specific functional responses. A crystal structure of a MART-1-specific γδ TCR, together with MHC/peptide, revealed distinctive but similar docking properties to those previously reported for αβ TCRs, recognizing MART-1 on HLA-A*0201. Our work shows that antigen-specific and MHC-restricted γδ T cells can be generated in vitro and that MART-1-specific γδ T cells can also be found and cloned from the naïve repertoire. These findings reveal that classical MHC-restricted human γδ TCRs exist in the periphery and have the potential to be used in developing of new TCR-based immunotherapeutic approaches.

PubMed: 30552102
DOI: 10.1126/sciimmunol.aav4036

Experimental method

X-RAY DIFFRACTION (2.75 Å)