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Abstracts (complete list) - Wissenschaft Online

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Annette Busch, Thomas Quast, Waldemar Kolanus, Percy Knolle, Andreas Limmer<br />

Transfer of T cell surface molecules to Dendritic cells upon T<br />

cell priming involving two distinct mechanisms differing in<br />

quality and time<br />

The adaptive immune response is initiated in secondary lymphoid organs by contact<br />

between antigen-presenting cells (APCs) and antigen-specific CD4+ T cells. This<br />

activation is characterized by multiple antigen recognition events that comprise the<br />

interaction of both cell types through various molecules. In addition to the exchange of<br />

costimulatory signals and cytokines the cells transfer cell surface molecules. To date<br />

this is reported only as a unidirectional process of transfer from APC surface molecules<br />

to the T cell. Here we describe for the first time the transfer of human and murine T cell<br />

surface receptors to the APC. This transfer occurs in two phases that differ in quality<br />

and time. The first set of molecules is transferred rapidly after T–APC contact, is cell–<br />

cell contact-dependent, bound in an acid wash-resistant form to the cell surface and<br />

resembles a mechanism described as trogocytosis, whereupon the APC actively gnaws<br />

membrane fragments from the T cell membrane. The second set of T cell molecules is<br />

exchanged after T cell activation (>16h), is non-covalently bound (acid wash sensitive)<br />

and is transferred in a cell–cell contact-independent mode, resembling molecule<br />

exchange via exosomes. The transferred molecules may have an important role in APC<br />

conditioning and immunoregulation since they include the T cell receptor (TCR), CD3<br />

and costimulatory molecules. Murine dendritic cells (DCs) loaded with T cell surface<br />

molecules from ovalbumin (OVA)-specific CD4+ T cells by antigen-specific interaction<br />

were less efficient in priming naïve CD4+ T cells of the same specificity. The great<br />

amount of transgenic TCR on the DC surface may be responsible for the reduced<br />

activation of the T cells by masking the antigen-bearing MHC molecules for access of<br />

following antigen-specific CD4+ T cells. These findings may indicate an important role of<br />

transferred T cell molecules to APC in the intraclonal competition of T cells for APC<br />

access.

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