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* Department of Pathology and Laboratory Medicine,
Department of Medicine, and
Jonsson Comprehensive Cancer Center, University of California Los Angeles School of Medicine, Los Angeles, CA 90095;
Department of Medicine, Division of Hematology Oncology, New England Medical Center, Boston, MA 02111;
¶ Department of Medicine and Department of Pathology and Immunology, Washington University, St. Louis, MO 63110; and
|| Glycobiology Program, Burnham Institute, La Jolla, CA 92307
Galectin-1 kills immature thymocytes and activated peripheral T cells by binding to glycans on T cell glycoproteins including CD7, CD45, and CD43. Although roles for CD7 and CD45 in regulating galectin-1-induced death have been described, the requirement for CD43 remains unknown. We describe a novel role for CD43 in galectin-1-induced death, and the effects of O-glycan modification on galectin-1 binding to CD43. Loss of CD43 expression reduced galectin-1 death of murine thymocytes and human T lymphoblastoid cells, indicating that CD43 is required for maximal T cell susceptibility to galectin-1. CD43, which is heavily O-glycosylated, contributes a significant fraction of galectin-1 binding sites on T cells, as T cells lacking CD43 bound 
50% less galectin-1 than T cells expressing CD43. Although core 2 modification of O-glycans on other glycoprotein receptors is critical for galectin-1-induced cross-linking and T cell death, galectin-1 bound to CD43 fusion proteins modified with either unbranched core 1 or branched core 2 O-glycans and expression of core 2 O-glycans did not enhance galectin-1 binding to CD43 on T cells. Moreover, galectin-1 binding clustered CD43 modified with either core 1 or core 2 O-glycans on the T cell surface. Thus, CD43 bearing either core 1 or core 2 O-glycans can positively regulate T cell susceptibility to galectin-1, identifying a novel function for CD43 in controlling cell death. In addition, these studies demonstrate that different T cell glycoproteins on the same cell have distinct requirements for glycan modifications that allow recognition and cross-linking by galectin-1.
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 by Grants CA33000 (to M.F.), HL58444 (to J.M.G.), and GM63281 (to L.G.B.) from the National Institutes of Health. J.D.H. was supported in part by National Institutes of Health National Research Service Award Predoctoral Fellowships T32 GM08042, CA009120, AI52031, by a University of California Dissertation Year Fellowship, and by the University of California Los Angeles Aesculapians. The Jonsson Comprehensive Cancer flow cytometry facility was supported by Grants CA16042 and AI 28697 from the National Institutes of Health. The BIAcore facility was supported by Grant RR019042 from the National Institutes of Health.
2 Address correspondence and reprint requests Dr. Linda G. Baum, Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, 10833 Le Conte Avenue, Los Angeles, CA 90095. E-mail address: lbaum{at}mednet.ucla.edu
3 Abbreviations used in this paper: C2GnT, core 2 N-acetylglucosaminyltransferase; CHO, Chinese hamster ovary; DP, double positive; PI, propidium iodide; Bmax, maximum binding capacity; PNA, peanut lectin agglutinin.
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