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Immunogenetics. 2018 Sep 17. doi: 10.1007/s00251-018-1078-y. [Epub ahead of print]

Thymus-specific serine protease, a protease that shapes the CD4 T cell repertoire.

Guerder S1,2,3,4, Hassel C5,6,7, Carrier A8.

Author information

1
INSERM, U1043, 31300, Toulouse, France. Sylvie.guerder@inserm.fr.
2
CNRS, UMR5282, 31300, Toulouse, France. Sylvie.guerder@inserm.fr.
3
Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, 31300, Toulouse, France. Sylvie.guerder@inserm.fr.
4
INSERM UMR1043, Centre de Physiopathologie de Toulouse Purpan, CHU Purpan, BP 3028, 31024, Toulouse CEDEX 3, France. Sylvie.guerder@inserm.fr.
5
INSERM, U1043, 31300, Toulouse, France.
6
CNRS, UMR5282, 31300, Toulouse, France.
7
Centre de Physiopathologie de Toulouse Purpan, Université Toulouse III Paul-Sabatier, 31300, Toulouse, France.
8
Aix-Marseille University, Inserm, CNRS, Institut Paoli-Calmettes, CRCM, Marseille, France.

Abstract

The lifespan of T cells is determined by continuous interactions of their T cell receptors (TCR) with self-peptide-MHC (self-pMHC) complexes presented by different subsets of antigen-presenting cells (APC). In the thymus, developing thymocytes are positively selected through recognition of self-pMHC presented by cortical thymic epithelial cells (cTEC). They are subsequently negatively selected by medullary thymic epithelial cells (mTEC) or thymic dendritic cells (DC) presenting self-pMHC complexes. In the periphery, the homeostasis of mature T cells is likewise controlled by the interaction of their TCR with self-pMHC complexes presented by lymph node stromal cells while they may be tolerized by DC presenting tissue-derived self-antigens. To perform these tasks, the different subsets of APC are equipped with distinct combination of antigen processing enzymes and consequently present specific repertoire of self-peptides. Here, we discuss one such antigen processing enzyme, the thymus-specific serine protease (TSSP), which is predominantly expressed by thymic stromal cells. In thymic DC and TEC, TSSP edits the repertoire of peptide presented by class II molecules and thus shapes the CD4 T cell repertoire.

KEYWORDS:

Autoimmunity; CD4 T cell tolerance; CD4 T cell-positive selection; Dendritic cells; Thymic epithelial cells; Thymus-specific serine protease (TSSP)

PMID:
30225612
DOI:
10.1007/s00251-018-1078-y

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