Chapter category: T-Cell Activation
Operation Enduring Costimulation: Modulation of B7 Receptors to Elicit Anti-Tumor Immunity
The B7-CD28 Family Molecules
Edited by: Lieping ChenISBN: 0-306-47842-0
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Chapter authors:
Eugene D. Kwon, Qingyong Ji and Arthur A. Hurwitz
In the war against the evil-doer tumor, the battle lines are clearly drawn. Marshalling the T cell infantry can be a powerful way to neutralize the enemy. The weaponry used by the assaulting immunoforces has been the focus of strategic planning for the past decade. The identification of the triggers that launch T cell-mediated immunity to a variety of tumors has led to considerable enthusiasm about the possibility of a successful attack on the evil neoplasm. Our understanding of the role of the critical costimulatory interactions during the activation of T cells has contributed to the development of many promising strategies for recruiting T cells to the on-going war on cancer. As described elsewhere, T cell activation requires at least two distinct signals resulting from interactions with antigen presenting cells (APCs). The first signal is antigen-specific, mediated by T cell receptor (TcR) occupancy by antigen/major histocompatibiliy complex (MHC) molecules. In the context of tumor immunity, this refers to recognition of a ‘tumor antigen’ at both the priming and effector stages. Also, to be destroyed by effector T cells, tumors must express detectable MHC. The second signal is antigen-independent and is referred to as a costimulatory signal. Initially, this signal was identified as CD28 ligation by B7-1 (CD80). Subsequently, B7-2 (CD86) was identified as an additional CD28 ligand and more recently, additional members of the CD80 and CD86 family have been reported. In general, expression of CD80 and CD86 (hereafter collectively referred to as B7) is largely restricted to professional APC’s (dendritic cells, macrophages, and B cells), and rarely expressed by tumor cells.
Additional chapters from this book:
Roles of NF-kB in Autoimmunity
Stacey Garrett and Youhai H. Chen
Autoimmune diseases are the result of improper and uncontrolled immune responses against self-antigens. The NF-kB/Rel family of transcription factors is known to play important roles in the initiati...
B7 Family of Costimulatory Molecules in the Induction and Regulation of Autoimmunity
Claudia Jabs, Arlene H. Sharpe and Vijay K. Kuchroo
Normally, most autoreactive T cells are deleted during thymic development. The autoreactive T cells, which escape thymic deletion are kept in check by the mechanisms of peripheral tolerance, which i...
B7-H3
Andrei I. Chapoval and Lieping Chen
Although members of the immunoglobulin superfamily (IgS) are involved in many physiological functions including molecular transport, cell adhesion, cytokine receptions, regulation of gene expression...
Role of ICOS in T Cell Activation
Jeffrey A. Ledbetter, Erik Espling and Martha Hayden-Ledbetter
Inducible costimulator (ICOS) was recently identified as a novel member of the CD28 family by Hutloff et al.1 A monoclonal antibody (mAb), F44, specific for human ICOS was generated by immunization ...
The ICOS/B7RP-1 Costimulation Pathway
Steven K. Yoshinaga
A novel costimulation pathway homologous to CD28/B7 has recently been discovered and characterized. The Inducible Costimulator (ICOS) is structurally and functionally homologous to CD28. The B7-Rela...
PD-1:PD-1 Ligand Pathway
Gordon J. Freeman and Arlene H. Sharpe
The PD-1:PD-1 ligand pathway is a new pathway within the B7:CD28 superfamily. This pathway consists of the PD-1 receptor and its two ligands PD-L1 (B7-H1) and PD-L2 (B7-DC).1-4 This chapter focuses ...
T Lymphocyte Signaling Pathways Regulated by CD28 and CTLA-4
David J. McKean and Matthew D. Griffin
T lymphocytes in peripheral lymphoid tissues are inactive cells that must receive receptor-initiated signals to become activated and participate in an antigen specific immune response. The integrati...
Structure Prediction and Binding Site Identification of the CD28 and B7 Family Molecules
Jürgen Bajorath
The focal point of this contribution is a critical evaluation of studies designed to explore structure-function relationships of CD28- and B7-like proteins prior to experimental determination of thr...
Negative Costimulatory Functions of B7-H1
Haidong Dong, Hideto Tamura, Sheng-Dian Wang and Lieping Chen
Costimulatory molecules B7-1 and B7-2 belong to an emerging family of the immunoglobulin (Ig) superfamily and share ~25% identical amino acid sequences concentrated in the Ig V- and Ig C-like extracel...
Costimulatory Molecules in T Cell Development, Activation and Effector Function: Similar Activity, Opposite Consequences
Yang Liu, Jian Xin Gao, Xue-Feng Bai, Xingluo Liu, Huiming Zhang and Pan Zheng
Costimulatory molecules were initially dubbed as the second signal determining the fate of naïve T cells after they were engaged by MHC:peptide complex. Accumulating evidence supports the notion that ...
The Role of B7s in Transplantation
Didier A. Mandelbrot, Wayne R. Godfrey, Arlene H. Sharpe and Bruce R. Blazar
The manipulation of the B7 family of molecules holds great promise for developing therapies to be used in clinical transplantation. A major goal in the field of transplan- tation immunology is to...
Operation Enduring Costimulation: Modulation of B7 Receptors to Elicit Anti-Tumor Immunity
Eugene D. Kwon, Qingyong Ji and Arthur A. Hurwitz
In the war against the evil-doer tumor, the battle lines are clearly drawn. Marshalling the T cell infantry can be a powerful way to neutralize the enemy. The weaponry used by the assaulting imm...
