Thymus-specific serine protease regulates positive selection of a subset of CD4+ thymocytes.
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.
Gommeaux
Julien
J
INSERM, U624 Stress cellulaire, Marseille, France.
Grégoire
Claude
C
Nguessan
Prudence
P
Richelme
Mireille
M
Malissen
Marie
M
Guerder
Sylvie
S
Malissen
Bernard
B
Carrier
Alice
A
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology*; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology*
D000949:Histocompatibility Antigens Class II; C472501:Prss16 protein, mouse; D012697:Serine Endopeptidases