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Journal of Virology, December 2008, p. 12241-12251, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01563-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans ^{, ,}

Erika Assarsson,¹ Huynh-Hoa Bui,¹ John Sidney,¹ Qing Zhang,¹ Jean Glenn,¹ Carla Oseroff,¹ Innocent N. Mbawuike,² Jeff Alexander,³ Mark J. Newman,³ Howard Grey,¹ and Alessandro Sette^1*

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California,¹ Viral Respiratory Pathogens Research Unit, Departments of Molecular Virology and Microbiology, Baylor College of Medicine, Dallas, Texas,² Pharmexa-Epimmune, San Diego, California³

Received 23 July 2008/ Accepted 22 September 2008

Continuing antigenic drift allows influenza viruses to escape antibody-mediated recognition, and as a consequence, the vaccine currently in use needs to be altered annually. Highly conserved epitopes recognized by effector T cells may represent an alternative approach for the generation of a more universal influenza virus vaccine. Relatively few highly conserved epitopes are currently known in humans, and relatively few epitopes have been identified from proteins other than hemagglutinin and nucleoprotein. This prompted us to perform a study aimed at identifying a set of human T-cell epitopes that would provide broad coverage against different virus strains and subtypes. To provide coverage across different ethnicities, seven different HLA supertypes were considered. More than 4,000 peptides were selected from a panel of 23 influenza A virus strains based on predicted high-affinity binding to HLA class I or class II and high conservancy levels. Peripheral blood mononuclear cells from 44 healthy human blood donors were tested for reactivity against HLA-matched peptides by using gamma interferon enzyme-linked immunospot assays. Interestingly, we found that PB1 was the major target for both CD4⁺ and CD8⁺ T-cell responses. The 54 nonredundant epitopes (38 class I and 16 class II) identified herein provided high coverage among different ethnicities, were conserved in the majority of the strains analyzed, and were consistently recognized in multiple individuals. These results enable further functional studies of T-cell responses during influenza virus infection and provide a potential base for the development of a universal influenza vaccine.

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* Corresponding author. Mailing address: La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. Phone: (858) 752-6916. Fax: (858) 752-6985. E-mail: alex{at}liai.org

Published ahead of print on 8 October 2008.

Kirin publication number 1036.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, December 2008, p. 12241-12251, Vol. 82, No. 24
0022-538X/08/$08.00+0     doi:10.1128/JVI.01563-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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