Dendritic cells sensitize TCRs through self-MHC-mediated Src family kinase activation.
It is unclear whether peptide-MHC class II (pMHC) complexes on distinct types of APCs differ in their capacity to trigger TCRs. In this study, we show that individual cognate pMHC complexes displayed by dendritic cells (DCs), as compared with nonprofessional APCs, are far better in productively triggering Ag-specific TCRs independently of conventional costimulation. As we further show, this is accomplished by the unique ability of DCs to robustly activate the Src family kinases (SFKs) Lck and Fyn in T cells even in the absence of cognate peptide. Instead, this form of SFK activation depends on interactions of DC-displayed MHC with TCRs of appropriate restriction, suggesting a central role of self-pMHC recognition. DC-mediated SFK activation leads to "TCR licensing," a process that dramatically increases sensitivity and magnitude of the TCR response to cognate pMHC. Thus, TCR licensing, besides costimulation, is a main mechanism of DCs to present Ag effectively.
Meraner
Paul
P
Research Center for Molecular Medicine, Austrian Academy of Sciences.
Horejsí
Václav
V
Wolpl
Alois
A
Fischer
Gottfried F
GF
Stingl
Georg
G
Maurer
Dieter
D
D017951:Antigen Presentation / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity; D002461:Cell Line, Transformed; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000276:immunology* / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000936:Antigen-Antibody Complex; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; C494960:Fyn protein, mouse; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051076:Proto-Oncogene Proteins c-fyn