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Preferential Use of B7.2 and Not B7.1 in Priming of Vaccinia Virus-Specific CD8 T Cells¹

Shahram Salek-Ardakani^2,*, Ramon Arens, Rachel Flynn^*, Alessandro Sette, Stephen P. Schoenberger^3, and Michael Croft^3,*

Divisions of ^* Molecular Immunology, Developmental Immunology, and Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

Recent studies have demonstrated that CD28 provides critical costimulatory signals required for optimal CD8 T cell expansion and effector function in response to several viruses, including influenza, HSV, and vaccinia virus (VACV). CD28 has two ligands expressed largely on professional APC, named B7.1 (CD80) and B7.2 (CD86). Although some results suggest that these ligands are equivalent and both promote CD28 signaling, it is not clear whether they are equally important for priming of antiviral T cells. Herein we show that B7.2 is critical for early CD8 T cell responses to both dominant and subdominant VACV epitopes, correlating with its strong induction on CD8⁺ dendritic cells. In contrast, B7.1 plays no significant role. Signals from an exogenously applied adjuvant can recruit B7.1 activity and lead to further enhanced priming of VACV-reactive CD8 T cells. However, during a natural infection, B7.1 is not functional, likely related to inefficient up-regulation or active suppression by VACV. These studies provide evidence that B7.2 is the major ligand for the CD28 receptor on VACV-specific CD8 T cells, that B7.2 can promote efficient CD8 T cell priming without B7.1, and that B7.1 and B7.2 can be differentially utilized during antiviral responses.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants AI77079 (to S.S.-A.), AI67341 (to M.C.), and CA081261 and AI076972 (to S.S.), as well as a Veni grant (916.56.155) from The Netherlands Organization for Scientific Research (to R.A.). This is publication 1056 from the La Jolla Institute for Allergy and Immunology.

² Address correspondence and reprint requests to Dr. S. Salek-Ardakani, Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, San Diego, CA 92037. E-mail address: ssalek{at}liai.org

³ S.P.S. and M.C. are joint senior authors.

⁴ Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; DC, dendritic cell; DN, double negative; VACV, vaccinia virus; VSV, vesicular stomatitis virus; WR, Western Reserve; WT, wild type.