Chapter category: T-Cell Activation
Role of ICOS in T Cell Activation
The B7-CD28 Family Molecules
Edited by: Lieping ChenISBN: 0-306-47842-0
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Chapter authors:
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 with activated T cells, and was used to isolate the ICOS antigen for immunochemistry studies. From the peptide sequence of ICOS, full length complementary DNA was isolated and found to encode a protein with 24% identity to CD28 and 17% identity to CTLA-4. Like CD28 and CTLA-4, ICOS is expressed as a disulfide-linked dimer with conserved cysteines critical for the formation of the inter-and intra-chain disulfide bonds that stabilize the structure of this molecular family.2 ICOS is not expressed by resting T cells, but is rapidly induced primarily on CD45 RO memory T cells following T cell activation. 1 Stimulation of T cells with mAb F44 increased T cell proliferation in response to suboptimal activation with anti-CD3 mAb, and increased the production of IL-10, IL-4, IL-5, TNFa, IFNg, and GM-CSF, but did not increase production of IL-2. ICOS costimulation also increased expression of CD25, CD69, and CD154 on activated T cells.1 Since the initial cloning of ICOS, there has been significant interest in defining the function of ICOS in the adaptive immune response and in identifying the potential for targeting of the ICOS pathway for pharmacological intervention in autoimmune disease and cancer. Figures 1 illustrate the CD28 family and the B7 family of known ligands with some of the key features of their function and regulation indicated.
Additional chapters from this book:
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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
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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
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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...
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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 ...
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