title: Distinct subsets of CD1d-restricted T cells recognize self-antigens loaded in different cellular compartments.
abstract: Although recent studies have indicated that the major histocompatibility complex-like, beta2-microglobulin-associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to alpha/beta T cells, little is known about the T cell subsets that interact with CD1. A subset of CD1d-autoreactive, natural killer (NK)1.1 receptor-expressing alpha/beta T cells has recently been identified. These cells, which include both CD4(-)CD8(-) and CD4(+) T cells, preferentially use an invariant Valpha14-Jalpha281 T cell receptor (TCR) alpha chain paired with a Vbeta8 TCR beta chain in mice, or the homologous Valpha24-JalphaQ/Vbeta11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)-gamma upon TCR engagement and may regulate a variety of infectious and autoimmune conditions. Here, we report the existence of a second subset of CD1d-restricted CD4(+) T cells that do not express the NK1.1 receptor or the Valpha14 TCR. Like the Valpha14(+) NK1.1(+) T cells, these T cells exhibit a high frequency of autoreactivity to CD1d, use a restricted albeit distinct set of TCR gene families, and contribute to the early burst of IL-4 and IFN-gamma induced by intravenous injection of anti-CD3. However, the Valpha14(+) NK1.1(+) and Valpha14(-) NK1.1(-) T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the Valpha14(+) NK1.1(+) cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the Valpha14(-) NK1.1(-) cells does not. These experiments suggest the existence of two phenotypically different subsets of CD1d-restricted T cells that survey self-antigens loaded in distinct cellular compartments.
authors.affiliation: Department of Molecular Biology, Princeton, New Jersey 08544, USA.
authors.forename: Y H
authors.initials: YH
authors.lastname: Chiu
authors.forename: J
authors.initials: J
authors.lastname: Jayawardena
authors.forename: A
authors.initials: A
authors.lastname: Weiss
authors.forename: D
authors.initials: D
authors.lastname: Lee
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: A
authors.initials: A
authors.lastname: Dautry-Varsat
authors.forename: A
authors.initials: A
authors.lastname: Bendelac
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D018949:Antigens, CD1 / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D011992:Endosomes / Q000378:metabolism; D006825:Hybridomas / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D018040:Receptors, Neurokinin-1 / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
chemical_list: D000941:Antigens; D018949:Antigens, CD1; D017252:CD3 Complex; D015704:CD4 Antigens; D011948:Receptors, Antigen, T-Cell; D018040:Receptors, Neurokinin-1; D015847:Interleukin-4; D007371:Interferon-gamma