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Thymus‐specific serine protease regulates positive selection of a subset of CD4 + thymocytes
Author(s) -
Gommeaux Julien,
Grégoire Claude,
Nguessan Prudence,
Richelme Mireille,
Malissen Marie,
Guerder Sylvie,
Malissen Bernard,
Carrier Alice
Publication year - 2009
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200839175
Subject(s) - biology , cd8 , mhc class ii , mhc class i , serine protease , t cell receptor , microbiology and biotechnology , major histocompatibility complex , transgene , mhc restriction , thymocyte , protease , immunology , t cell , gene , genetics , antigen , immune system , biochemistry , enzyme
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.