Glycodelin A triggers T cell apoptosis through a novel calcium-independent galactose-binding lectin activity.
Glycodelin A (GdA) is one of the progesterone inducible endometrial factors that protect the fetal semi-allograft from maternal immune rejection. The immunoregulatory effects of GdA are varied, with diverse effects on the fate and function of most immune cell types. Its effects on T cells are particularly relevant as it is capable of regulating T cell activation, differentiation, as well as apoptosis. We have previously reported that GdA triggers mitochondrial stress and apoptosis in activated T cells by a mechanism that is distinct and independent of its effects on T cell activation. In this study we describe the characterization of a cell surface receptor for GdA on T cells. Our results reveal a novel calcium-independent galactose-binding lectin activity of GdA, which is responsible for its apoptogenic function. This discovery adds GdA to a select group of soluble immunoregulatory lectins that operate within the feto-placental compartment, the only other members being the galectin family proteins. We also report for the first time that both CD4(+) and CD8(+) T cell subsets are equally susceptible to inhibition with GdA, mediated by its novel lectin activity. We demonstrate that GdA selectively recognizes complex-type N-linked glycans on T cell surface glycoproteins, and propose that the galectin-1 glycoprotein receptor CD7 maybe a novel target for GdA on T cells. This study, for the first time, links the lectin activity of GdA to its biological function.
SundarRaj
Swathi
S
Department of Biochemistry, Indian Institute of Science, Bangalore, India.
Soni
Chetna
C
Karande
Anjali A
AA
D000818:Animals; D019011:Antigens, CD7 / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002417:Cattle; D005260:Female; D005333:Fetus / Q000276:immunology; D037483:Galectin 1 / Q000276:immunology*; D000071816:Glycodelin; D006023:Glycoproteins / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000276:immunology*; D008928:Mitochondria / Q000276:immunology; D010920:Placenta / Q000276:immunology; D011257:Pregnancy Proteins / Q000276:immunology*
D019011:Antigens, CD7; D037483:Galectin 1; D000071816:Glycodelin; D006023:Glycoproteins; C445499:LGALS1 protein, human; C045246:PAEP protein, human; D011257:Pregnancy Proteins