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KMID : 0620920100420050353
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Experimental & Molecular Medicine
2010 Volume.42 No. 5 p.353 ~ p.365
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Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis
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Park Hyo-Jin
Ban Young-Larn
Byun Da-Hye
Park Seong-Hoe
Jung Kyeong-Chaeon
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Abstract
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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 TCRα-/- 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.
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KEYWORD
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apoptosis, CD99 antigen, mouse, PILR protein, mouse, T cell receptor, thymocyte
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