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Infiltrating the immunological synapse: prospects for the use of altered peptide ligands for the treatment of immune pathology

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The Immune Synapse as a Novel Target for Therapy

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

For many years, T cell activation was thought to lack finesse, engagement of the T cell receptor (TCR) resulting in the full spectrum of responses and changes in gene expression associated with activation. The inflexibility of such an all-or-nothing response provided few strategies for intervention in ongoing immune pathology, the most effective approach being the prevention of TCR engagement by MHC blockade. The use of surrogate peptides to compete for binding with the pathogenic epitope relied solely on their high affinity for the relevant MHC restriction element rather than any similarity in sequence to the pathogenic epitope [1]. The first description of altered peptide ligands (APL) therefore served as a turning point in understanding of T cells and their mode of antigen recognition, and suggested alternative approaches to immune intervention that relied on use of ligands that differ almost imperceptibly from the wild-type epitope, guaranteeing their recognition by the relevant T cells.

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Authors and Affiliations

  1. Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK

    Paul J. Fairchild

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  1. Paul J. Fairchild
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  1. Unidade de Imunologia Celular Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-208, Lisboa, Portugal

    Luis Graca

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Fairchild, P.J. (2008). Infiltrating the immunological synapse: prospects for the use of altered peptide ligands for the treatment of immune pathology. In: Graca, L. (eds) The Immune Synapse as a Novel Target for Therapy. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8296-4_3

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