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* Research Center for Molecular Medicine, Austrian Academy of Sciences,
Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, and
Department of Blood Group Serology, Medical University of Vienna, Vienna, Austria;
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; and
¶ Laboratory for Medical Genetics, Martinsried, Germany
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.
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1 This work was supported by Grants SFB F18/13 and SFB F23/08 from the Research Center for Molecular Medicine, the Austrian Science Foundation, and by Project no. AV0Z50520514 from the Academy of Sciences of the Czech Republic.
2 Address correspondence and reprint requests to Dr. Dieter Maurer, Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. E-mail address: dieter.maurer{at}meduniwien.ac.at
3 Abbreviations used in this paper: DC, dendritic cell; iDC, immature DC; mDC, mature DC; SFK, Src family kinase; pMHC, peptide MHC class II; HSA, human serum albumin; TT, tetanus toxoid; TSST-1, toxic shock syndrome toxin-1.
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