Characterization of HLA class II/peptide-TCR interactions of the immunodominant T cell epitope in Art v 1, the major mugwort pollen allergen.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Beatrice Jahn-SchmidBarbara Bohle

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 1(25-36) (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 restriction element for Art v 1(25-36)-specific T cell responses. Further assessment of binding of Art v 1(25-36) to artificial HLA-DR molecules revealed that its affinity was high for HLA-DR1. Amino acid I27 was identified as anchor residue interacting with DR molecules in pocket P1. Additionally, Art v 1(25-36) bound with high affinity to HLA-DRB1*0301 and *0401, moderately to HLA-DRB1*1301 and HLA-DRB5*0101, and weakly to HLA-DRB1*1101 and *1501. T cell activation was also inducible by Art v 1(25-36)-loaded, APC-expressing HLA molecules other than DR1, indicating degeneracy of peptide binding and promiscuity of TCR recognition. Specific binding of HLA-DRB1*0101 tetramers containing Art v 1(19-36) allowed the identificatio...Continue Reading

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Citations

May 13, 2011·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·W R Thomas
Jun 24, 2014·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·P Moingeon
Oct 26, 2012·Human Vaccines & Immunotherapeutics·Marek JutelSylwia Smolinska
Nov 26, 2010·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·E WambreP Moingeon
Feb 17, 2018·Allergy, Asthma, and Clinical Immunology : Official Journal of the Canadian Society of Allergy and Clinical Immunology·Qing MiaoLi Xiang

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