Negative Co-Receptors and Ligands (eBook)

Contents 6
Contributors 8
TIM-3 and Its Regulatory Role in Immune Responses 10
1 Introduction 11
2 Protein Structure 11
3 TIM-3 Ligands 13
3.1 Identification of Galectin-9 as a TIM-3 Ligand 13
3.2 Phosphatidylserine as a TIM-3 Ligand 14
3.3 Carbohydrate Ligands for TIM-3 15
4 Expression of TIM-3 15
4.1 Transcriptional Control of TIM-3 Expression 16
5 TIM-3 in Disease 16
5.1 Genetic Basis for Role of TIM-3 in Disease 16
6 TIM-3 in Autoimmune Diseases 17
6.1 TIM-3 in Chronic Viral Infection 18
6.2 TIM-3 in Other Diseases 20
7 Conclusions 20
References 21
Role of PD-1 in Regulating T-Cell Immunity 25
1 Identification of PD-1 and Its Ligands 26
2 Structure of PD-1 and Its Ligands 27
3 Regulation of PD-1 Expression 29
4 PD-1 Signaling: Molecular Mechanisms of Inhibition 30
5 Biological Significance of PD-1 32
5.1 PD-1 in Autoimmunity 32
5.2 PD-1 in Chronic Viral Infection 34
5.3 PD-1 in Antitumor Immunity 35
6 Conclusions 37
References 38
The Role of IL-10 in Regulating Immunity to Persistent Viral Infections 46
1 Introduction 47
1.1 Immune Dynamics During Acute and Persistent Virus Infection: The Failure of Antiviral Immunity 47
2 The Impact of Host-Based Regulatory Mechanisms in T Cell Exhaustion 49
2.1 Discovery That Host-Based Suppressive Factors Inhibit Clearance of Persistent Viral Infection 49
2.2 Multiple Regulatory Factors Suppress T Cell Responses During Viral Persistence 50
2.3 Differential Impact of Reversing T Cell Exhaustion During Viral Persistence 51
3 The Impact of IL-10 Toward Viral Persistence 52
3.1 The Diverse Roles of IL-10 During Viral Infection 52
3.2 Sources, Mechanisms, and Targets of IL-10 During Persistent Viral Infection 54
4 Targeting Immunosuppression: Potential Therapeutic Applications for Blocking IL-10 60
5 Past, Present, and Future 64
References 65
Inhibitory Ly49 Receptors on Mouse Natural Killer Cells 73
1 Introduction 74
2 Ly49 Haplotypes and Ligands 74
3 Inhibitory Signaling Events 80
4 Educational Impact of Ly49 Receptors on NK Cells 82
5 Inhibitory Ly49 Receptors and Viral Infections 84
6 Inhibitory Ly49 Receptors in Transplantation and Malignancy 85
7 Concluding Remarks 87
References 87
Immunoregulatory Roles for Fc Receptor-Like Molecules 94
1 Introduction 95
2 Identification of FCRL Molecules Reveals a New Level of B Cell Regulation 95
3 FCRL Structural Properties 96
4 FCRL Expression Patterns 99
5 FCRL Functional Properties 101
6 FCRL Involvement in Human Diseases 103
7 Concluding Remarks 105
References 106
FcgammaRs in Health and Disease 110
1 Introduction 111
2 The Family of Canonical Fcgamma-Receptors 112
3 Regulation of IgG Activity In Vivo 114
4 Influence of Antibody Glycosylation and Novel Fcgamma-Receptors 116
5 Role of FcgammaRs for Infection 118
6 Microbial Immune Escape Mechanisms Targeting the IgG-FcgammaR Interaction 121
7 Other Ligands for Fcgamma-Receptors 122
8 Conclusions 123
References 124
TGF-beta Function in Immune Suppression 131
1 Introduction 132
2 TGF-beta and Signal Transduction 132
3 How TGF-beta Inhibits Immune Responses 133
4 Induction and Regulation of Treg-Differentiation by TGF-beta 135
5 Molecular Mechanism of Foxp3 Induction by TGF-beta 137
6 TGF-beta and Th17 Differentiation 138
7 Regulation of Effector Th-Differentiation by TGF-beta 139
8 Treg Is a Major Source of Pro-TGF-beta, and TGF-beta Is One of the Effector Molecules of Tregs 139
9 Smad-Dependent and Smad-Independent Regulation of Th Differentiation by TGF-beta 140
10 Smad-Mediated Suppression of the Cytokine Production 142
11 Reciprocal Regulation of TGF-beta Signaling and IFN-gamma Signaling 143
12 Conclusions 144
References 145
Index 152