title: Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis.
abstract: Here, we show that the interaction between two membrane proteins, the mouse homologue of CD99 (designated D4) and its ligand, paired immunoglobulin-like type 2 receptor (PILR), is one of the major mechanisms of thymocyte apoptosis. Using the polymeric fusion protein of PILR and IgG1 (PILR-Ig), we demonstrated that D4 ligation in the absence of T cell receptor (TCR) engagement leads to the induction of apoptosis, mainly at the double-positive stage of thymocytes. This was further confirmed by a blocking study in which blocking the interaction between D4 and PILR by soluble D4 protein led to reduced apoptosis in the fetal thymic organ culture with wild type and TCRalpha(-/-) mice. Furthermore, the dissection of intracellular signaling pathway demonstrated that D4 cross-linking led to caspase activation without any change in mitochondrial membrane potential. Based on these data, we propose a mechanism for thymocyte depletion in which the interaction between D4 and PILR delivers an active signal.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Young Larn
authors.initials: YL
authors.lastname: Ban
authors.forename: Dahye
authors.initials: D
authors.lastname: Byun
authors.forename: Seong Hoe
authors.initials: SH
authors.lastname: Park
authors.forename: Kyeong Cheon
authors.initials: KC
authors.lastname: Jung
mesh_terms: D000071443:12E7 Antigen; D000818:Animals; D030801:Animals, Genetically Modified; D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000071443:12E7 Antigen; D015703:Antigens, CD; C522605:Cd99 protein, mouse; C548037:PILRalpha protein, mouse; C548038:PILRbeta protein, mouse; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic