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* Institute of Molecular Medicine and Experimental Immunology (IMMEI) and
Life and Medical Sciences (LIMES) Institute, University of Bonn, Bonn, Germany; and
Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany
Activation of CD4+ T cells by APCs occurs by multiple Ag recognition events including the exchange of costimulatory signals and cytokines. Additionally, the T cells acquire APC-derived surface molecules. Herein, we describe for the first time the transfer of human and murine T cell surface receptors to APCs after Ag-specific interaction. This transfer occurs in two qualitatively different phases. The first group of molecules (e.g., CD2) derived from the T cell surface was transferred rapidly after 2 h of interaction, was strongly bound on the DC surface (acid wash-resistant), was strictly dependent on dendritic cell-T cell contact, and transferred independently of T cell activation. The second group, including the CD3/TCR complex, CD27, and OX40, was of intracellular origin, transferred later after 10–16 h in a cell-cell contact-independent fashion, was noncovalently bound, and was strictly dependent on Ag-specific T cell activation. Functionally, murine dendritic cells that received TCR molecules from OVA-specific CD4+ T cells after Ag-specific interaction were less efficient in priming naive CD4+ T cells of the same specificity without losing their ability for CD8+ T cell stimulation, indicating that the transferred TCR molecules mask the Ag-bearing MHC II molecules, thereby reducing their accessibility to following Ag-specific CD4+ T cells. While the first group of transferred T cell surface molecules might facilitate the detachment of the CD4+ T cell from the dendritic cell during the early scanning phases, the second group could play an important immunomodulatory role in intraclonal competition of T cells for APC access, making the physical presence of CD4+ T cells unnecessary.
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1 This work was supported by a Lise-Meitner Stipend to A.B. and SFB704 to A.L.
A.B. designed and performed the research, analyzed the data, and wrote the paper. A.L. coordinated and designed the research and revised the paper. T.Q. provided substantial help for confocal microscopy experiments and confocal data analysis. W.H. is the head of the Life and Medical Sciences (LIMES) Institute where all confocal microscopy experiments were performed, and he thereby provided essential equipment; he further coordinated the research and revised the paper. S.K. designed and performed substantial research for the characterization of the intracellularly mediated transfer. P.A. coordinated the research for the intracellularly mediated transfer and revised the paper. P.K. is the head of the Institute of Molecular Medicine and Experimental Immunology where all experiments except confocal microscopy experiments were performed, and he thereby provided essential equipment and facilities; he further coordinated the research and revised the paper.
2 Address correspondence and reprint requests Dr. Andreas Limmer, or Dr. Annette Busch, Institute of Molecular Medicine and Experimental Immunology (IMMEI), Sigmund-Freud-Strasse 25, University of Bonn, Bonn 53105, Germany. E-mail addresses: annette.busch{at}ukb.uni-bonn.de and andreas.limmer{at}uni-bonn.de
3 Abbreviations used in this paper: DC, dendritic cell; SEB, staphylococcal enterotoxin B superantigen.
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