Mechanisms Of Lymphocyte Activation And Immune Regulation Vii

Proceedings of the Seventh International Conference held in New Port Beach, California, February 6-8, 1998

During the past 5 years rapid progress has been made in the understanding of biochemical pathways for signal transduction in lymphocyte activation. Gene cloning technology has been instrumental in defining and making available in pure form of a number of growth and differentiation factors, in the characterization of their receptors, and in the delineation of genes for the T cell receptor. This book is divided into 6 sections. Section 1 deals with the molecular structure of the T cell receptor. Section 2 discusses the role of the T cell receptor, membrane ion channels and biochemical pathways of signal transduction in T cell activation. The molecular structures and biological and immunological effects of interleukin 1, interleukin 2 and interleukin 3 are presented in Section 3. This section also details the structure of interleukin 2 receptor and its use as a target for therapy for certain leukemias. Section 4 includes the biochemical events which occur following the delivery of the signal for B cell activation, proliferation, and differentiation by antigen, growth/differentiation factors. The molecular structure of B cell stimulating factors is also discussed. The role of oncogene expression in cellular activation and differentiation is included in Section 5. The cellular and molecular basis of natural killing and the molecular basis of cyc1osporin A-mediated immunosuppression are discussed in detail in Section 6. We hope this book will serve as a reference work on basic mechanisms of lymphocyte activation, proliferation, and differentiation for immunologists and molecular biologists.

The ac ti vati on of Iymphocytes by physiologie ligands has become a central area of study for immunologists. Furthermore, Iymphocytes offer many advantages for the study of general aspects of receptor-mediated cellular activation. For these reasons, research on the cellular and molecular aspects of the activation of Iymphocytes by antigens, antigen analogues, Iymphokines and other growth factors has expanded enormously in the last several years. Aseries of conferences, "The International Conferences on Lymphocyte Activation", has been initiated to meet the growing need for a forum for the discussion of the topics that are included within the area of Iymphocyte activation. This volume represents the proceedings of the Second International Conference on Lymphocyte Activation and Immune Regulation, held on February 18-20, 1988 at Newport Beach, California. The proceedings comprise four major sections. The first deals with the T cell receptors and T cell activation. It includes a model for the T cell receptor interaction with a complex of MHC plus antigen, structure of y c'i T cell receptor and their distinct isotypic forms, the role of zeta chain in the expression and structure of T cell receptors and its role in transmembrane signalling. The use of somatic cell mutants in the study of signal transduction function of the T cell antigen receptors and the early and late steps of signal transduction via a / ß T cell antigen receptors are discussed.

This volume is edited by Dr. Sudhir Gupta, internationally recognized expert in Immunology, Professor of Medicine, Pathology, Microbiology and Molecular Genetics. Topics include toll receptors, dendritic cells, NK cells, and complement receptors.

Signaling through antigen receptor initiates a complex series of events resulting in the activation of genes that regulate the development, proliferation and differentiation of lymphocytes. During the past few years, rapid progress has been made in understanding the molecular basis of signaling pathways mediated by antigen and cytokine receptors. These pathways involve protein tyrosine kinases which are coupled to downstream regulatory molecules, including small guanine nucleotide binding proteins (e. g. p21'OS), serine threonine kinases (e. g. , members of the ERK family), and a large group of transcription factors. More recently, there have been breakthroughs in elucidating the genetic defects underlying three X-linked primary immunodeficiency diseases in humans. This volume surveys aspects of these rapidly developing areas of research. The book is divided into 5 different sections. Section I deals with signaling pathways in B lymphocytes. It includes a contemporary assessment of B cell antigen receptor structures, and discussion of the role of Ig-a/lg-B polypeptides in linking the antigen receptor to intracellular signal transduction pathways. The role of accessory molecules in the regulation of signaling by the B cell antigen receptor is also considered. Section II adopts a similar approach to the analysis of the antigen receptor on T lymphocytes. The importance of specialized signaling motifs in the CD3 polypeptides, mechanisms whereby these motifs may interact with the lymphocyte-specific protein tyrosine kinases, and the downstream consequences of these interactions are reviewed. In addition, the role of antigen-induced apoptosis in the generation of immunological tolerance is discussed.

In recent years rapid progress has been made in the areas of T cell and B cell biology, cell-cell and cell-matrix/stroma interactions. The use of isolated subunits of the T cell receptor invariant chains has been instrumental in defining their role in signal transduction and tyrosine phosphorylation. A role of src family phosphotyrosine kinases in T cell activation has been demonstrated and several phosphotyrosine kinase substrates have been identified and their functions characterized. Homologous recombinant techniques have led to the development of murine strains that lack CD4 or CD8 expression. These models are likely to be instrumental in studying the role of T cell subsets in autoimmune disorders, tissue transplant rejection and tumor rejection. A role of major histocompatibility complex I in the development of T cell subsets and NK cells has been defined. Recent data suggest a role of interaction between plasma membrane molecules of activated T helper cells and B cells, B cells primed with plasma membrane of activated T helper cells and cytokines, and interaction between bone marrow stromal cells and B cell progenitors and precursors, in the B cell development, proliferation, and differentiation. The structure and functions of adhesion molecules, especially with regard to signal transduction and homing events, are better defined.