The B7-CD28 Family Molecules

by Lieping Chen (Editor)

Overview

The B7-CD28 family molecules are probably the most intensively studied receptor-ligand systems in the field of immunology. This is evident from the explosive accumulation of literature, particularly in the last ten years. Recent years have witnessed rapid discoveries and characterization of new receptors and ligands in the family. These new pathways, although still in their infancy, have already brought much excitement to the field. However, until now, there has been no single volume to cover this entire area. This book was created to bring together state-of-the-art information and critical thinking from the leading investigators. This book covers significant territory of this rapidly moving field from structural biology and biochemical signalling to immunological functions and their potential applications in the treatment of human diseases. This is an excellent handbook and reference for immunologists, health professionals as well as medical students and graduate students in life science field.

Product Details

ISBN-13:	9781441934123
Publisher:	Springer US
Publication date:	12/06/2010
Series:	Molecular Biology Intelligence Unit
Edition description:	Softcover reprint of hardcover 1st ed. 2003
Pages:	141
Product dimensions:	6.14(w) x 9.21(h) x 0.24(d)

Table of Contents

	Preface	ix
1.	Structure Prediction and Binding Site Identification of the CD28 and B7 Family Molecules	1
	Abstract	1
	The CD28 and B7 Families: Mediators of T Cell Costimulation	1
	The CD28 and B7 Families and the Immunoglobulin Superfamily	2
	Sequences, Topology and Binding Characteristics	2
	Structure-Function Analysis Based on Comparative Protein Models and Mutagenesis	4
	Comparative Modeling of IgSF Proteins Sharing Low Sequence Similarity	5
	Molecular Models of CTLA-4 and CD80/CD86	6
	Mapping of Binding Sites	7
	Experimentally Determined Structures	8
	Evaluation of Predictions	9
	Conclusions	9
2.	T Lymphocyte Signaling Pathways Regulated by CD28 and CTLA-4	12
	Introduction	12
	CD28 Costimulation	13
	CTLA-4 Signaling	23
3.	Costimulatory Molecules in T Cell Development, Activation and Effector Function: Similar Activity, Opposite Consequences	38
	Abstract	38
	Conceptual Evolution and Molecular Basis of the Second Signal for T Cell Activation	38
	Multiplicity of Costimulatory Molecules	39
	Expanding the Horizon of T Cell Costimulation: From Activation to Effector Function	39
	Costimulatory Molecules in T Cell Development	40
	Negative Costimulation? Paradigm Revisited	42
	B71/2 Mediated Costimulation in T Cell Activation and Development: Similar Activity, Opposite Consequences	42
4.	Negative Costimulatory Functions of B7-H1	48
	Introduction	48
	Molecular Structure and Expression of B7-H1	48
	Counter-Receptor of B7-H1	50
	Immunological Functions of B7-H1	51
	Effect of Tumor-Associated B7-H1 in Immune Evasion	52
	Reverse Signaling of B7-H1 to Regulate T Cell Responses	54
	Conclusion	55
5.	PD-1:PD-1 Ligand Pathway	59
	Introduction	59
	Structure and Expression of the PD-1 Receptor	59
	Function of PD-1	60
	Biochemistry Basis for PD-1 Function	61
	Structure and Expression of PD-1 Ligands	62
	Function of PD-1 Ligands	63
	Summary and Concluding Remarks	65
6.	The ICOS/B7RP-1 Costimulation Pathway	67
	Abstract	67
	Introduction	67
	Terminology	68
	Structures of ICOS and B7RP-1	68
	ICOS Expression	69
	B7RP-1 Expression	69
	Cytokine Regulation by ICOS/B7RP-1	70
	Immunoglobulin Regulation by ICOS/B7RP-1	72
	CD28 and CTLA-4 Regulate, but Are Not Required for, ICOS Function	72
	The HpH4 HIV Antigen Is ICOS	72
	ICOS and Apoptosis	73
	B7RP-1-Fc and B7.2-Fc Transgenic Mice Exhibit Intestinal Inflammation	73
	ICOS/B7RP-1 Therapeutic Modalities	74
	Anti-Tumor Activities of B7RP-1	74
	ICOS Blockade in Transplantation	75
	ICOS Regulation of Secondary and Recall Responses	75
	EAE Studies Reveal the Promise and the Complexity of ICOS/B7RP-1 Regulation	76
	Differential ICOS/B7RP-1 Regulation	77
	Summary	77
7.	Role of ICOS in T Cell Activation	82
	Introduction	82
	Defective T Cell Help for Isotype Class Switching in ICOS Deficient Mice	82
	Identification of a Novel ICOS Ligand Related to CD80	84
	Role of ICOS in CD4 T Cell Activation	84
	ICOS Costimulation of CD8 T Cells	87
8.	B7-H3	91
	Introduction	91
	Molecular and in Silico Cloning of B7-H3	91
	Isoforms of Human B7-H3	92
	B7-H3 Gene Analysis	93
	B7-H3 Tissue Distribution and Expression of B7-H3R on Activated T Cells	94
	B7-H3 Costimulates T Cell Growth in Vitro	96
	B7-H3 Selectively Increases IFN-[gamma] Production	97
9.	The Role of B7s in Transplantation	100
	Introduction	100
	The Absence of B7 Costimulation Renders T Cells Anergic in Vitro	100
	Blockade of B7 Molecules Prolongs Organ Graft Survival	101
	Allorecognition Pathways Affected by B7 Costimulation	101
	The Role of B7 Molecules in Chronic Graft Rejection	102
	Role of B7 in Xenotransplantation	102
	The Role of B7-1 versus B7-2 Mediated Costimulation in Transplantation Responses	104
	Combination Approaches to Improve Allograft Survival Based upon B7:CD28/CTLA-4 Blockade	104
	CTLA4 Signaling Prolongs Graft Survival	105
	B7 and CD28 Homologues	106
	Overview of ex Vivo Blockade of the CD28/CTLA-4:B7 Pathway for Graft-versus-Host Disease (GVHD) Prevention	106
	Ex Vivo Blockade of B7:CD28/CTLA-4 Interactions in Human Mixed Lymphocyte Reaction (MLR) Cultures	107
	Human Clinical Trial of ex Vivo B7:CD28/CTLA4 Blockade for GVHD Prevention	107
	Adjuvants to B7 Blockade	108
	Modifications of ex Vivo B7:CD28/CTLA4 Costimulatory Pathway Blockade of Human MLR Cultures Designed to Improve the Efficacy of Tolerization	109
	Ex Vivo Tolerization of Murine MLR Cultures by Costimulatory Pathway Blockade As a Means of Achieving GVHD Prevention	109
	In Vivo Blockade of B7:CD28/CTLA4 for GVHD Prevention	110
	Mechanism(s) of GVHD Inhibition by B7:CD28/CTLA-4 Blockade	111
	Role of CD28/CTLA-4:B7 in Graft-versus-Leukemia (GVL)	112
	Role of CD28/CTLA-4:B7 in Alloengraftment	112
	Future Directions	113
10.	B7 Family of Costimulatory Molecules in the Induction and Regulation of Autoimmunity	118
	Introduction	118
	EAE and IDDM	119
	Manipulation of B7 Costimulatory Pathway	120
	Blocking Negative Costimulatory Signals in Autoimmune Diseases	122
	ICOS-B7h Costimulation in Autoimmune Diseases	123
	PD-1:PD-L1/PD-L2 Pathway and Autoimmunity	124
11.	Operation Enduring Costimulation: Modulation of B7 Receptors to Elicit Anti-Tumor Immunity	128
	Turning Up the Offensive	128
	An Alliance of Mediators	130
	Shutting Down the Defense	131
	The New Breed	133
	Future Battles	134
	Index	139