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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0900404v1 183/2/1055    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by DeFord-Watts, L. M. Articles by van Oers, N. S. C. PubMed PubMed Citation Articles by DeFord-Watts, L. M. Articles by van Oers, N. S. C.

The Cytoplasmic Tail of the T Cell Receptor CD3 Subunit Contains a Phospholipid-Binding Motif that Regulates T Cell Functions¹

Laura M. DeFord-Watts^*, Tara C. Tassin, Amy M. Becker^*, Jennifer J. Medeiros^*, Joseph P. Albanesi, Paul E. Love^¶, Christoph Wülfing^*, and Nicolai S. C. van Oers^2,*,

^* Department of Immunology, Department of Pharmacology, Department of Microbiology, and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390; and ^¶ Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892

The CD3 subunit of the TCR complex contains two defined signaling domains, a proline-rich sequence and an ITAM. We identified a third signaling sequence in CD3 , termed the basic-rich stretch (BRS). Herein, we show that the positively charged residues of the BRS enable this region of CD3 to complex a subset of acidic phospholipids, including PI(3)P, PI(4)P, PI(5)P, PI(3,4,5)P₃, and PI(4,5)P₂. Transgenic mice containing mutations of the BRS exhibited varying developmental defects, ranging from reduced thymic cellularity to a complete block in T cell development. Peripheral T cells from BRS-modified mice also exhibited several defects, including decreased TCR surface expression, reduced TCR-mediated signaling responses to agonist peptide-loaded APCs, and delayed CD3 localization to the immunological synapse. Overall, these findings demonstrate a functional role for the CD3 lipid-binding domain in T cell biology.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by grants from the National Institutes of Health T32 AI005284 (to A.B. and L.D.), AI42953, and AI71229 (to N.S.C.v.O.).

² Address correspondence and reprint requests to Nicolai S. C. van Oers, Room NA2.200, 6000 Harry Hines Boulevard, Department of Immunology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9093. E-mail address: nicolai.vanoers{at}utsouthwestern.edu

³ Abbreviations used in this paper: PRS, proline-rich sequence; PI(3)P, phosphatidylinositol-3-phosphate; PI(4)P, phosphatidylinositol 4-monophosphate; PI(5)P, phosphatidylinositol 5-phosphate; PI(4,5)P₂, phosphatidylinositol 4,5-bisphosphate; BRS, basic-rich stretch; PC, phosphatidylcholine; DN, CD4^–CD8^– double negative; DP, CD4⁺CD8⁺ double positive; SP, CD4⁺ or CD8⁺ single positive; LAT, linker for activation of T cell; MFI, mean fluorescent intensity.

⁴ The online version of this article contains supplemental material.