Multichain Immune Recognition Receptor Signaling (eBook)

ALEXANDER SIGALOV, PhD, is a Research Assistant Professor in the Department of Pathology at the University of Massachusetts Medical School in Worcester, Massachusetts, USA. His main research interests include protein intrinsic disorder and oligomericity in the context of transmembrane signal transduction, the molecular mechanisms underlying immune receptor-mediated signaling and ways to control these processes and thus to modulate the immune response, as well as the development and applications of novel targets and strategies for innovative immune therapy. He discovered and investigated a very unusual and unique biophysical phenomenon, the homooligomerization of intrinsically disordered proteins, thus providing the first evidence for the existence of specific interactions between unfolded protein molecules. In the field of immunology, he unraveled a long-standing mystery of transmembrane signaling and immune cell activation triggered by multichain immune recognition receptors. Later, he developed a novel concept of platelet inhibition and invented a novel class of platelet inhibitors. In the field of immune therapy, he proposed new therapeutic strategies for a variety of malignancies and immune disorders, including immunodeficiencies, inflammatory and autoimmune diseases, allergy and HIV. He is a member of the American Association for the Advancement of Science and the Biophysical Society, USA. Alexander Sigalov received his academic degrees (MSc in Chemistry and a PhD in Organic Chemistry) from Moscow State University, Russia.

DEDICATION 6
FOREWORD 7
PREFACE 9
ABOUT THE EDITOR... 11
PARTICIPANTS 12
CONTENTS 17
ACKNOWLEDGEMENTS 24
T- Cell Receptor 25
B- Cell Receptor 36
Fc Receptors 46
Natural Killer Cell Receptors 59
Platelet Glycoprotein VI 77
Clustering Models 88
Segregation Models 98
Kinetic Proofreading Model 106
Serial Triggering Model 119
Conformational Model 127
Permissive Geometry Model 137
Signaling Chain Homooligomerization ( SCHOOL) Model 145
Visualization of Cell- Cell Interaction Contacts— Synapses and Kinapses 188
Visualization of Protein Interactions in Living Cells 207
Immunogenicity in Peptide- Immunotherapy 222
Therapeutic Application of Transmembrane T and Natural Killer Cell Receptor Peptides 232
Fc Receptor Targeting in the Treatment of Allergy, Autoimmune Diseases and Cancer 244
Therapeutic Blockade of T- Cell Antigen Receptor Signal Transduction and Costimulation in Autoimmune Disease 258
MHC and MHC- Like Molecules 276
SCHOOL Model and New Targeting Strategies 292
Immune Receptor Signaling, Aging and Autoimmunity 336
Viral Pathogenesis, Modulation of Immune Receptor Signaling and Treatment 349
INDEX 374