Chapter category: T-Cell Activation
B7 Family of Costimulatory Molecules in the Induction and Regulation of Autoimmunity
The B7-CD28 Family Molecules
Edited by: Lieping ChenISBN: 0-306-47842-0
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Chapter authors:
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 include clonal anergy and active suppression. Autoimmune diseases do not occur until there is appropriate activation, expansion and differentiation of autoreactive T cells in the peripheral immune compartment. In the organ specific autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes, the T cells have to migrate across the blood brain barrier/blood tissue barrier to access the target organ. In the target tissues the autoreactive T cells have to be further activated by the local antigen presenting cells (APCs) to initiate inflammation and mediate tissue injury.1 Consistent with the two-signal model, autoreactive T cells in the periphery do not become activated until they encounter antigen (either self or mimicry non-self peptide) in the context of relevant MHC molecules, together with appropriate costimulatory signals (as discussed below). Activation of T cells is important at several stages of induction of an autoimmune disease, including stimulation and clonal expansion within peripheral lymphoid tissues, entry and reactivation of autoreactive T cells into the target tissue to initiate tissue destruction within tissue parenchyma of the target tissue (for a review, see ref. 2). Therefore, expression of appropriate costimulatory molecules on the antigen presenting cells in the peripheral immune compartment and also at the target tissue site is essential for the induction and effector functions of the autoreactive T cells and induction of autoimmune disease.
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...
