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Immunol. 2002. 091806 Copyright c 2002 by Annual Reviews. All rights reserved THE B7 FAMILY OF LIGANDS AND ITS RECEPTORS: Annu. Rev. Immunol. 20:29-53. org by HINARI on 09/01/07. For personal use only. New Pathways for Costimulation and Inhibition of Immune Responses Beatriz M. com Key Words ICOS, PD-1, PD-L, T cell activation, tolerance ■ Abstract T cell activation is dependent upon signals delivered through the antigen-specific T cell receptor and accessory receptors on the T cell. A primary costimulatory signal is delivered through the CD28 receptor after engagement of its ligands, B7-1 (CD80) or B7-2 (CD86).

The crystal structures of the CTLA-4/B7-1 and CTLA-4/B7-2 complexes implicate the MYPPPY site as the major contact site in CTLA-4 with B7-1 and B7-2 (12, 13). Although the structure of CD28 has not yet been solved, amino acid homologies, mutation data, and modeling support the concept that this motif will also be a major B7-binding site for CD28 (19). The related FDPPPF site in ICOS is not sufficiently conserved to allow for detectable binding of ICOS to B7-1 or B7-2 (16, 20, 21). However, structural homology raises the possibility that this motif might be important in the binding of ICOS to its ligand, which is a member of the B7 family (see below).

Org by HINARI on 09/01/07. For personal use only. NEW B7-LIKE LIGANDS AND RECEPTORS 37 production (32). This deficit could be overcome by the use of CFA as an adjuvant (32). However, in another study, immunization with KLH in CFA also resulted in decreased isotype switching (34), suggesting that the precise immunization conditions and antigen used may affect the outcome. Immunization of mice with NP-OVA in alum (34) or with aerosolized antigen in the lung (33) also revealed a deficit in IgE production in ICOS-deficient mice.

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Annual Review of Immunology Volume 20 2002 by Annual Reviews

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