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Ya-Hui Chiu^*, Jayanthi Jayawardena^*, Angela Weiss^*, Daniel Lee^*, Se-Ho Park^*, Alice Dautry-Varsat, and Albert Bendelac^*

From the ^* Department of Molecular Biology, Princeton, New Jersey 08544; and the Institut Pasteur, Unite de Biologie des Interactions Cellulaires, 75724 Paris Cedex 15, France

Although recent studies have indicated that the major histocompatibility complex–like, β2-microglobulin–associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to /β 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 /β T cells has recently been identified. These cells, which include both CD4^–CD8^– and CD4⁺ T cells, preferentially use an invariant V14-J281 T cell receptor (TCR) chain paired with a Vβ8 TCR β chain in mice, or the homologous V24-JQ/Vβ11 in humans. This cell subset can explosively release key cytokines such as interleukin (IL)-4 and interferon (IFN)- 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 V14 TCR. Like the V14⁺ 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- induced by intravenous injection of anti-CD3. However, the V14⁺ NK1.1⁺ and V14^– NK1.1^– T cells differ markedly in their requirements for self-antigen presentation. Antigen presentation to the V14⁺ NK1.1⁺ cells requires endosomal targeting of CD1d through a tail-encoded tyrosine-based motif, whereas antigen presentation to the V14^– 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.

Key Words: CD1 • self-antigen • endosome • interleukin 4 • interferon

Abbreviations used: HPRT, hypoxanthine ribosyl transferase; mfi, mean fluorescent intensity; RT, reverse transcriptase.

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This article has been cited by other articles:

• Shinkai, K., Locksley, R. M. (2000). Cd1, Tuberculosis, and the Evolution of Major Histocompatibility Complex Molecules. JEM 191: 907-914 [Full Text]  

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