title: Galectin-1 binds different CD43 glycoforms to cluster CD43 and regulate T cell death.
abstract: 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 approximately 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles School of Medicine, Los Angeles, CA 90095, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Hernandez
authors.forename: Julie T
authors.initials: JT
authors.lastname: Nguyen
authors.forename: Jiale
authors.initials: J
authors.lastname: He
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Blair
authors.initials: B
authors.lastname: Ardman
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Green
authors.forename: Minoru
authors.initials: M
authors.lastname: Fukuda
authors.forename: Linda G
authors.initials: LG
authors.lastname: Baum
mesh_terms: D000818:Animals; D016923:Cell Death / Q000276:immunology; D037483:Galectin 1 / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D051917:Leukosialin / Q000737:chemistry / Q000378:metabolism*; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology
chemical_list: D037483:Galectin 1; D051917:Leukosialin; D008562:Membrane Glycoproteins; D011134:Polysaccharides