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Immunity. 2005 Jul;23(1):29-40.

The kinetic stability of MHC class II:peptide complexes is a key parameter that dictates immunodominance.

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1
David H. Smith Center for Vaccine Biology and Immunology, Aab Institute of Biomedical Sciences, Department of Microbiology and Immunology, University of Rochester, Rochester, New York 14642, USA.

Abstract

T cell priming to exogenous antigens reflects regulated antigen processing in dendritic cells, subsequent homing to lymph nodes, sustained interactions between T cells and antigen-bearing dendritic cells, and, ultimately, selective T cell activation and differentiation. In this study, we test the hypothesis that an intrinsic property of the class II:peptide complex is a key determinant that dictates the specificity of an emerging CD4 T cell response. We found that immunodominant peptides possess extremely long half-lives with class II molecules (t(1/2) > 150 hr), whereas cryptic peptides displayed half-lives of less than 10 hr. Furthermore, and most importantly, by using a peptide shuttle vector and four independent antigens, we demonstrate a direct, causative relationship between the half-life of peptide epitopes and their immunogenicity in vivo. Taken collectively, our results suggest the half-life of class II:peptide complexes is the primary parameter that dictates the ultimate hierarchy of the elicited T cell response.

PMID:
16039577
DOI:
10.1016/j.immuni.2005.05.009
[Indexed for MEDLINE]
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