Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes

Eur J Immunol. 2009 Apr;39(4):956-64. doi: 10.1002/eji.200839175.

Abstract

Thymus-specific serine protease (TSSP) was initially reported as a putative protease specifically expressed in the endosomal compartment of cortical thymic epithelial cells (cTEC). As such, TSSP is potentially involved in the presentation of the self-peptides that are bound to MHC class II molecules expressed at the cTEC surface and are involved in the positive selection of CD4(+) thymocytes. We tested this hypothesis by generating mutant mice deprived of Prss16, the gene encoding TSSP. TSSP-deficient mice produced normal numbers of T cells, despite a decrease in the percentage of cTEC expressing high surface levels of MHC class II. By using sensitive transgenic models expressing MHC class II-restricted TCR transgenes (Marilyn and OT-II), we showed that the absence of TSSP markedly impaired the selection of Marilyn and OT-II CD4(+) T cells. In contrast, selection of CD8(+) T cells expressing an MHC class I-restricted TCR transgene (OT-I) was unaffected. Therefore, TSSP is involved in the positive selection of some CD4(+) T lymphocytes and likely constitutes the first serine protease to play a function in the intrathymic presentation of self-peptides bound to MHC class II complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / enzymology
  • CD4-Positive T-Lymphocytes / immunology*
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Histocompatibility Antigens Class II / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / immunology*
  • Thymus Gland / enzymology
  • Thymus Gland / immunology*

Substances

  • Histocompatibility Antigens Class II
  • Prss16 protein, mouse
  • Serine Endopeptidases