J. Exp. Med., Volume 189, Number 1, January 4, 1999 103-110

Distinct Subsets of CD1d-restricted T Cells Recognize Self-antigens Loaded in Different Cellular Compartments

By 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, 2-microglobulin-associated CD1 molecules might function to present a novel chemical class of antigens, lipids and glycolipids, to / 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 / T cells has recently been identified. These cells, which include both CD4CD8 and CD4⁺ T cells, preferentially use an invariant V14-J281 T cell receptor (TCR)  chain paired with a V8 TCR  chain in mice, or the homologous V24-JQ/V11 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.

CD1;  self-antigen;  endosome;  interleukin 4;  interferon

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