The half-life of the T-cell receptor/peptide-major histocompatibility complex interaction can modulate T-cell activation in response to bacterial challenge.
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.
Carreño
Leandro J
LJ
Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Bueno
Susan M
SM
Bull
Paulina
P
Nathenson
Stanley G
SG
Kalergis
Alexis M
AM
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology; D006207:Half-Life; D008213:Lymphocyte Activation / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016297:Mutagenesis, Site-Directed; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology
D000942:Antigens, Bacterial; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin