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Immunodominance of CD4 T Cells to Foreign Antigens Is Peptide Intrinsic and Independent of Molecular Context: Implications for Vaccine Design¹

David H. Smith Center for Vaccine Biology and Immunology, AaB Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642

Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to Ag processing play a major role in determining a peptide’s ability to recruit CD4 T cells. Implicit in these models is the prediction that the molecular context in which an antigenic peptide is contained will impact significantly on its immunodominance. In this study, we present evidence that the selectivity of CD4 T cell responses to peptides contained within protein Ags is not detectably influenced by the location of the peptide in a given protein or the primary sequence of the protein that bears the test peptide. We have used molecular approaches to change the location of peptides within complex protein Ags and to change the flanking sequences that border the peptide epitope to now include a protease site, and find that immunodominance or crypticity of a peptide observed in its native protein context is preserved. Collectively, these results suggest immunodominance of peptides contained in complex Ags is due to an intrinsic factor of the peptide, based upon the affinity of that peptide for MHC class II molecules. These findings are discussed with regard to implications for vaccine design.

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 the National Institutes of Health Grants R01AI51542 and HHSN 266200700008C, which were awarded to A.J.S.

² Address correspondence and reprint requests to Dr. Andrea J. Sant, David H. Smith Center for Vaccine Biology and Immunology, AaB Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642. E-mail address: andrea_sant{at}urmc.rochester.edu

³ Abbreviations used in this paper: LACK, Leishmania homolog of receptors for activated C kinase; ANS, 8-anilino-1-naphthalenesulfonic acid; HA, hemagglutinin; HEL, hen egg lysozyme; WT, wild type.

This article has been cited by other articles:

				J. M. Weaver, F. A. Chaves, and A. J. Sant Abortive activation of CD4 T cell responses during competitive priming in vivo PNAS, May 26, 2009; 106(21): 8647 - 8652. [Abstract] [Full Text] [PDF]