It is now accepted that T cell activation by an antigen-presenting cell requires the organization of a supramolecular structure the immune synapse. This structure, with different types of molecules spatially segregated, is involved in the delivery of quantitative and qualitative signals critical for T cell activation, and therefore in controlling the nature of the immune response. This volume discusses the progress in manipulating components of the immune synapse as a strategy to regulate the immune response in immune pathology, such as transplantation, autoimmunity and allergy. Donnadieu reviews the current knowledge on the molecular composition and organization of the immune synapse and how the formation of this structure can be modulated by chemokines. It is also known that the immune synapse formation is critical for the activation of naive T cells, as well as their functional polarization. The second chapter discusses the conversion of naive T cells into regulatory T cells (Treg) when components of the immune synapse are manipulated in such a way that the T cells receive suboptimal activation signals.

Discusses how interfering with T cell activation may lead to immune tolerance Describes immune modulation and the recruitment of regulatory T cells Provides information on the role of monoclonal antibodies in tolerance induction Describes mechanisms maintaining dominant tolerance Includes supplementary material: sn.pub/extras

Klappentext

The immune synapse can be compared to a molecular machine that controls T cell activation when getting in contact with an antigen-presenting cell (APC). The immune synapse is involved in the transfer of information across the T cellAPC junction. It plays an essential role in the control and nature of the immune response.

In recent years several approaches have been developed to reprogram the immune response by targeting molecules involved in the immune synapse. Monoclonal antibodies, such as those targeting the lymphocyte co-receptor, costimulatory and adhesion molecules (CD3, CD4, CD40L, CTLA4-Ig, LFA-1), or altered peptide ligands have been shown capable of inducing immune tolerance in transplantation, autoimmunity and allergy.

This volume discusses the progress in the field, from basic science to clinical trials, and the major mechanisms involved. It is of interest to clinicians and researchers working in this area.

Inhalt
The immune synapse and T cell activation: regulation by chemokines.- The induction of regulatory T cells by targeting the immune synapse.- Infiltrating the immunological synapse: prospects for the use of altered peptide ligands for the treatment of immune pathology.- Targeting CD4 for the induction of dominant tolerance.- Anti-CD3: from T cell depletion to tolerance induction.- Immune modulation by CD40L blockade.- CTLA-4-immunoglobulin and indoleamine 2,3-dioxygenase in dominant tolerance.- Adhesion molecules as therapeutic targets.- E3 ubiquitin ligases and immune tolerance: Targeting the immune synapse from within?.- FOXP3 biochemistry will lead to novel drug approaches for vaccines and diseases that lack suppressor T cells.- Transforming growth factor-?: From its effect in T cell activation to a role in dominant tolerance.- From mice to men: the challenges of developing tolerance-inducing biological drugs for the clinic.