Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis

Exp Mol Med. 2010 May 31;42(5):353-65. doi: 10.3858/emm.2010.42.5.037.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 12E7 Antigen
  • Animals
  • Animals, Genetically Modified
  • Antigens, CD / metabolism*
  • Apoptosis / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology*

Substances

  • 12E7 Antigen
  • Antigens, CD
  • Cd99 protein, mouse
  • PILRalpha protein, mouse
  • PILRbeta protein, mouse
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic