Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA.

Publication Type:

Journal Article


Proceedings of the National Academy of Sciences of the United States of America, Volume 108, Issue 6, p.2414-9 (2011)


2011, Basic Sciences Division, Center-Authored Paper, Clinical Research Division, Complementarity Determining Regions, Crystallography, X-Ray, Histocompatibility Antigens Class I, Humans, Immunity, Innate, Neoplasms, NK Cell Lectin-Like Receptor Subfamily K, Protein Structure, Quaternary, Receptors, Antigen, T-Cell, gamma-delta, T-Lymphocytes, Virus Diseases


γδ T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human γδ T cells of the V(δ)1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V(δ)1 γδ T-cell receptor (TCR) showed expected overall structural homology to antibodies, αβ, and other γδ TCRs, but complementary determining region conformations and conservation of V(δ)1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on γδ T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of γδ T-cell/target cell interfaces.