MICA engagement by human Vgamma2Vdelta2 T cells enhances their antigen-dependent effector function.
Vgamma2Vdelta2 T cells comprise 2%-5% of human peripheral blood T cells, recognize ubiquitous nonpeptide antigens, and expand up to 50-fold during microbial infection. It is not clear why these Vgamma2Vdelta2 T cells expand only after microbial infection. We show here that the stress-inducible molecule, MICA, is induced on the surface of dendritic and epithelial cells by infection with M. tuberculosis in vitro and in vivo. MICA engagement by the activating receptor, NKG2D, present on Vgamma2Vdelta2 T cells, resulted in a substantial enhancement of the TCR-dependent Vgamma2Vdelta2 T cell response to nonpeptide antigens and protein superantigens alike. Thus, a MICA-NKG2D interaction may be necessary for an effective innate immune response to microbe-associated antigens that also are constitutively present in vivo.
Das
H
H
Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital and, Harvard Medical School, Boston, MA 02115, USA.
Groh
V
V
Kuijl
C
C
Sugita
M
M
Morita
C T
CT
Spies
T
T
Bukowski
J F
JF
D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006801:Humans; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology; D055607:Receptors, Natural Killer Cell; D013601:T-Lymphocytes / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology
D016207:Cytokines; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell