2008
DOI: 10.4049/jimmunol.181.5.3636
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Characterization of HLA Class II/Peptide-TCR Interactions of the Immunodominant T Cell Epitope in Art v 1, the Major Mugwort Pollen Allergen

Abstract: More than 95% of mugwort pollen-allergic individuals are sensitized to Art v 1, the major allergen in mugwort pollen. Interestingly, the CD4 T cell response to Art v 1 involves only one single immunodominant peptide, Art v 125–36 (KCIEWEKAQHGA), and is highly associated with the expression of HLA-DR1. Therefore, we investigated the molecular basis of this unusual immunodominance among allergens. Using artificial APC expressing exclusively HLA-DRB1*0101 and HLA-DRA*0101, we formally showed that DR1 acts as rest… Show more

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Cited by 21 publications
(23 citation statements)
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“…Although the T cell response to Art v 1 25-36 is clearly associated with HLA-DR1, we previously found Art v 1 25-36 –specific T cells restricted by HLA-DR3, -DR16 or -DR15 in the minor fraction of DR1-negative patients [10]. Accordingly, the peptide showed degenerate high affinity binding to several HLA-DR alleles [10].…”
Section: Introductionmentioning
confidence: 99%
“…Although the T cell response to Art v 1 25-36 is clearly associated with HLA-DR1, we previously found Art v 1 25-36 –specific T cells restricted by HLA-DR3, -DR16 or -DR15 in the minor fraction of DR1-negative patients [10]. Accordingly, the peptide showed degenerate high affinity binding to several HLA-DR alleles [10].…”
Section: Introductionmentioning
confidence: 99%
“…14 Using a large panel of Art v 1-specific T-cell lines generated from peripheral blood (PB) of patients with mugwort allergy, we have identified a single immunodominant epitope, Art v 1 [25][26][27][28][29][30][31][32][33][34][35][36] , that is preferentially presented by HLA-DRB1*01. [15][16][17] Moreover, we have recently cloned and characterized an Art v 1-specific T-cell receptor (TCR), which allows us to investigate cell fate and phenotype decisions in PB T cells of individuals without allergy instead of using repeatedly stimulated T-cell lines or clones from individuals with allergy. 18 To the best of our knowledge, this is the first description of artificially induced, HLA class II restricted microvesicles (VLPs) able to modulate allergen-specific T-lymphocyte responses.…”
mentioning
confidence: 99%
“…Over the last decades, many studies have aimed to unravel the mechanisms of immunodominance. Among the hypotheses considered are intrinsic structural features of protein antigens12345, sensitivity to proteases67891011, epitope affinity for MHC class II12, T cell precursor frequency13, T cell receptor affinity for peptide/MHC II14151617, contributions from HLA-DM or H-2M in mice (DM, from now on)18192021, and contributions from HLA-DO or H-2O in mice (DO, from now on)222324. However, due to the complexity of the antigen processing pathway, pointing to a single mechanism as the driving force behind immunodominance has proved difficult.…”
mentioning
confidence: 99%