Abstract
BackgroundCD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens.MethodsThe published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy.ResultsEpitopes associated with allergy tended to be excluded from and lie adjacent to flexible segments of the allergen.ConclusionDuring the initiation of allergy, the N- and/or C-terminal ends of proteolytic processing intermediates were preferentially loaded into antigen presenting proteins for the priming of CD4+ T cells.
Highlights
CD4+ T-cell epitope immunodominance is not adequately explained by peptide selectivity in class II major histocompatibility proteins, but it has been correlated with adjacent segments of conformational flexibility in several antigens
CD4+ T-cell responses to dominant epitopes of protein allergens drive the development of allergic responses
The epitope specificity of CD4+ T cells varies greatly among individuals; but when analyzed for a population, the dominance of certain epitopes becomes apparent, with some dominant epitopes recognized by a majority of subjects
Summary
The published T-cell responses to two venom allergens and two aeroallergens were used to construct profiles of epitope dominance, which were correlated with the distribution of conformational flexibility, as measured by crystallographic B factors, solvent-accessible surface, COREX residue stability, and sequence entropy. In the study by Bohle et al, the specificity of T-cell lines or T-cell clones from 13 allergic individuals were mapped using a series of 12-mer peptides spanning the complete sequence of Ves v 5 with 9-residue overlaps [2]. This density of coverage results in exceptionally good resolution of epitope positions. In order to properly represent the sampling frequency of Ves v 5 epitope-mapping data, the significance tests were applied to paired datasets from which two-thirds of the points had been removed by retaining every third point
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