The molecular makeup and function of regulatory and effector synapses.
Physical interactions between T cells and antigen-presenting cells (APCs) form the basis of any specific immune response. Upon cognate contacts, a multimolecular assembly of receptors and adhesion molecules on both cells is created, termed the immunological synapse (IS). Very diverse structures of ISs have been described, yet the functional importance for T-cell differentiation is largely unclear. Here we discuss the principal structure and function of ISs. We then focus on two characteristic T-cell-APC pairs, namely T cells contacting dendritic cells (DCs) or naive B cells, for which extremely different patterns of the IS have been observed as well as fundamentally different effects on the function of the activated T cells. We provide a model on how differences in signaling and the involvement of adhesion molecules might lead to diverse interaction kinetics and, eventually, diverse T-cell differentiation. We hypothesize that the preferred activation of the adhesion molecule leukocyte function-associated antigen-1 (LFA-1) and of the negative regulator for T-cell activation, cytotoxic T-lymphocyte antigen-4 (CTLA-4), through contact with naive B cells, lead to prolonged cell-cell contacts and the generation of T cells with regulatory capacity. In contrast, DCs might have evolved mechanisms to avoid LFA-1 overactivation and CTLA-4 triggering, thereby promoting more dynamic contacts that lead to the preferential generation of effector cells.
Reichardt
Peter
P
Junior Research Group Immunodynamics, Helmholtz Centre for Infection Research, Braunschweig, Germany.
Dornbach
Bastian
B
Gunzer
Matthias
M
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D015398:Signal Transduction; D013569:Synapses / Q000276:immunology* / Q000378:metabolism*