The thymus specific serine protease or TSSP was identified in the late 90’s by two different laboratories1,2. It is the third member of the S28 group of serine proteases, the first member being Prolyl Carboxypeptidase (PRCP) and the second the dipeptidyl peptidase II (DPPII). It is named a serine protease with respect to its suspected enzymatic activity due to the presence of three amino acids (Serine, Aspartate and Histidine) in regions highly similar to the ones forming the catalytic site of PRCP.3,4
PRSS16, the gene encoding TSSP is predominantly expressed in the cortical thymic epithelial cells (cTEC) and to a lesser extend in different immunologically relevant tissues.1,2,4,5 In cTEC TSSP localizes in endosomes, where it possibly plays a role as a protease in the class II presentation pathway that shapes, by yet unknown mechanisms, the peptide repertoire presented by TEC and DC in the thymus.6
TSSP has been associated with different auto-immune diseases like diabetes mellitus type I, where mouse experiments showed a protective effect of TSSP absence. This protective effect is probably due to the impaired thymic selection of CD4+ T cells specific for islet antigens.5
We are currently trying to express the recombinant human TSSP protein, this can help us elucidate the enzymatic activity and other characteristics of this protein.
Literature
- Guerder S, Hassel C, Carrier A. Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire. Immunogenetics Vol. 71, Springer Verlag p.223–232 (2019).
- Viret C, Leung-Theung-Long S, Serre L, Lamare C, Vignali DAA, Malissen B, et al. Thymus-specific serine protease controls autoreactive CD4 T cell development and autoimmune diabetes in mice. J Clin Invest 121(5):1810–21 (2011).
- Boehm T. The adaptive phenotype of cortical thymic epithelial cells. Eur J Immunol 39(4):944–7 (2009).
- Cheunsuk S, Sparks R, Noveroske JK, Hsu T, Justice MJ, Gershwin ME, et al. Expression, genomic structure and mapping of the thymus specific protease Prss16: A candidate gene for insulin dependent diabetes mellitus susceptibility. J Autoimmun 18(4):311–6 (2002).
- Bowlus CL, Ahn J, Chu T, Gruen JR. Cloning of a novel MHC-encoded serine peptidase highly expressed by cortical epithelial cells of the thymus. Cell Immunol 196(2):80–6 (1999).Carrier A, Nguyen C, Victorero G, Granjeaud S, Rocha D, Bernard K, et al. Differential gene expression in CD3ε-and RAG1-deficient thymuses: definition of a set of genes potentially involved in thymocyte maturation. Immunogenetics Vol. 50, Springer-Verlag (1999).