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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: jimmunol.0901617v1 183/10/6432    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Cusick, M. F. Articles by Eckels, D. D. PubMed PubMed Citation Articles by Cusick, M. F. Articles by Eckels, D. D.

In Vitro Responses to Avian Influenza H5 by Human CD4 T Cells¹

Division of Histocompatibility and Immunogenetics, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132

To address the question of whether human T cells are capable of recognizing novel isolates of influenza virus, in vitro responses to recombinant Ags and synthetic peptides derived from the sequences of H1, H3, and H5 were examined in a cohort of 64 individuals selected from a healthy blood donor population. Humans respond in vitro to H1 and H3 following exposure through natural infection and vaccination. Responses to H5 were well correlated with those to H1 or H3, and thus, a significant repertoire of H5-responsive T cells is present in many individuals; clear nonresponders to H1, H3, and H5, however, do exist. Differences were observed in the cytokine responses to H1, H3, and H5, whereas both IL-2 and IFN- production characteristic of memory responses were observed for H1 and H3, and H5-specific responses elicited primarily IL-2 and little or no IFN-, consistent with a naive T cell phenotype. Responses to all influenza HA were restricted by HLA-DR molecules. To address the structural basis for T cell recognition of H1 and H5, overlapping synthetic peptides were used to identify epitopes and to determine whether recognition of H5 was limited to homologous sequences in H1, the most closely related HA phylogenetically. Although responses were generally correlated, no complete structural overlap was observed. These results suggest that helper T cell cross reactivity between different influenza strains may impart cross-protection to H5N1 strain of influenza.

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 grant U19 AI062627 from the National Institute for Allergy and Immunology Diseases, National Institutes of Health.

² Both authors contributed equally to this work.

³ Address correspondence and reprint requests to Dr. David D. Eckels, Division of Histocompatibility and Immunogenetics, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84132. E-mail address: david.eckels{at}path.utah.edu

⁴ Abbreviations used in this paper: HA, hemagglutinin; Io, ionomycin; SFC, spot-forming cell; SI, stimulation index.

⁵ The online version of this article contains supplemental material.