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The half-life of the T-cell receptor/peptide-major histocompatibility complex interaction can modulate T-cell activation in response to bacterial challenge
- Source :
- Immunology. 121(2)
- Publication Year :
- 2007
-
Abstract
- T-cell activation results from engagement of the T-cell receptor (TCR) by cognate peptide-major histocompatibility complex (pMHC) complexes on the surface of antigen-presenting cells (APC). Previous studies have provided evidence supporting the notion that the half-life of the TCR/pMHC interaction and the density of pMHC on the APC are two parameters that can influence T-cell activation. However, whether the half-life of the TCR/pMHC interaction can modulate T-cell activation in response to a pathogen challenge remains unknown. To approach this question, we generated strains of bacteria expressing variants of the ovalbumin (OVA) antigen, carrying point mutations in the SIINFEKL sequence. When bound to H-2K(b), this peptide is the cognate ligand for the OT-I TCR. Variants of the H-2K(b)/SIINFEKL bind to the OT-I TCR with distinct half-lives. Here we show that dendritic cells (DCs) infected with bacteria expressing OVA variants were incapable of activating OT-I T cells when the half-life of the TCR/H-2K(b)/OVA interaction was excessively short. Consistent with these data, T-cell activation was only observed in mice infected with bacteria expressing OVA variants that bound to OT-I with a half-life above a certain threshold. Considered together, our data suggest that the half-life of TCR/pMHC interaction can significantly modulate T-cell activation in vivo, as well as influence recognition of antigens expressed by bacteria. These observations underscore the importance of the TCR/pMHC half-life on the clearance of pathogens.
- Subjects :
- Salmonella typhimurium
Ovalbumin
T cell
Immunology
Receptors, Antigen, T-Cell
chemical and pharmacologic phenomena
Major histocompatibility complex
Lymphocyte Activation
Major Histocompatibility Complex
Mice
Antigen
medicine
Immunology and Allergy
Animals
Receptor
Antigens, Bacterial
biology
Point mutation
T-cell receptor
Dendritic Cells
Original Articles
Ligand (biochemistry)
Cell biology
Mice, Inbred C57BL
medicine.anatomical_structure
Salmonella Infections
biology.protein
Mutagenesis, Site-Directed
Half-Life
Subjects
Details
- ISSN :
- 00192805
- Volume :
- 121
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Immunology
- Accession number :
- edsair.doi.dedup.....eabecef2addf5aad9f117cd89ebf195c