title: Transcription profiling of Prss16 (Tssp) can be used to find additional peptidase genes that are candidates for self-peptide generation in the thymus.
abstract: Positive selection (PS) in the thymus involves the presentation of self-peptides that are bound to MHC class II on the surface of cortical thymus epithelial cells (cTECs). Prss16 gene corresponds to one important element regulating the PS of CD4(+) T lymphocytes, which encodes Thymus-specific serine protease (Tssp), a cTEC serine-type peptidase involved in the proteolytic generation of self-peptides. Nevertheless, additional peptidase genes participating in the generation of self-peptides need to be found. Because of its role in the mechanism of PS and its expression in cTECs, the Prss16 gene might be used as a transcriptional marker to identify new genes that share the same expression profile and that encode peptidases in the thymus. To test this hypothesis, we compared the differential thymic expression of 4,500 mRNAs of wild-type (WT) C57BL/6 mice with their respective Prss16-knockout (KO) mutants by using microarrays. From these, 223 genes were differentially expressed, of which 115 had known molecular/biological functions. Four endopeptidase genes (Casp1, Casp2, Psmb3 and Tpp2) share the same expression profile as the Prss16 gene; i.e., induced in WT and repressed in KO while one endopeptidase gene, Capns1, features opposite expression profile. The Tpp2 gene is highlighted because it encodes a serine-type endopeptidase functionally similar to the Tssp enzyme. Profiling of the KO mice featured down-regulation of Prss16, as expected, along with the genes mentioned above. Considering that the Prss16-KO mice featured impaired PS, the shared regulation of the four endopeptidase genes suggested their participation in the mechanism of self-peptide generation and PS.
authors.affiliation: Molecular Immunogenetics Group, Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, SP, 14040-900, Brazil.
authors.forename: Thaís A
authors.initials: TA
authors.lastname: Fornari
authors.forename: Márcia M
authors.initials: MM
authors.lastname: Marques
authors.forename: Catherine
authors.initials: C
authors.lastname: Nguyen
authors.forename: Alice
authors.initials: A
authors.lastname: Carrier
authors.forename: Geraldo A
authors.initials: GA
authors.lastname: Passos
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004847:Epithelial Cells / Q000201:enzymology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058977:Molecular Sequence Annotation; D010455:Peptides / Q000276:immunology*; D010802:Phylogeny; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*; D014158:Transcription, Genetic
chemical_list: D010455:Peptides; C472501:Prss16 protein, mouse; D012697:Serine Endopeptidases