Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis.
10.3858/emm.2010.42.5.037
- Author:
Hyo Jin PARK
1
;
Young Larn BAN
;
Dahye BYUN
;
Seong Hoe PARK
;
Kyeong Cheon JUNG
Author Information
1. Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea. jungkc66@snu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
apoptosis;
CD99 antigen, mouse;
PILR protein, mouse;
T cell receptor;
thymocyte
- From:Experimental & Molecular Medicine
2010;42(5):353-365
- CountryRepublic of Korea
- Language:English
-
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.
