Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens

Clin Exp Allergy. 2015 Oct;45(10):1601-12. doi: 10.1111/cea.12507.

Abstract

Background: Allergens from house dust mites (HDM) are a common cause of asthma. Der p and Der f from Dermatophagoides sp. are strong immunogens in humans. Allergen extracts are used to study T helper (Th2) cell responses to HDM, which are implicated in the development and regulation of allergic disease.

Objective: To define an epitope mixture that recapitulates, and might substitute for, HDM extract in terms of detecting and characterizing Th2 cell responses.

Methods: Peripheral blood mononuclear cells (PBMC) from 52 HDM allergic and 10 non-allergic individuals were stimulated with HDM extracts and assayed with a set of 178 peptides spanning mite allergens group Der p 1, 2, 23 and Der f group 1 and 2 allergens. A pool of the most dominant T cell epitopes identified in the present study and from published literature was assembled and tested for ex vivo T cell responses. Correlation with HDM-specific IgE titres was examined.

Results: Patterns of T cell reactivity to Der p and Der f - derived peptides revealed a large number of epitopes. Clear patterns of immunodominance were apparent, with HDM allergen group 1 and 2 dominant over group 23. Furthermore, within a given antigen, 6-11 epitopes accounted for the vast majority of responses. Based on these results and published data, a comprehensive dust mite pool (DMP) of epitopes was designed and found to allow detection of ex vivo T cell responses. DMP ex vivo reactivity correlated with HDM-specific IgE titres and was similar to that detected with commonly used HDM extracts. Ex vivo DMP stimulation was associated with a predominant Th2 response in allergic donors, and minor reactivity of T cells producing IFNγ, IL17 and IL10.

Conclusions & clinical relevance: A detailed map of Der p and Der f antigens defined a pool of epitopes that can be used to detect ex vivo HDM responses.

Keywords: T cell reactivity; dust mite allergy; epitope identification.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asthma / immunology*
  • Asthma / pathology
  • Epitope Mapping*
  • Epitopes, T-Lymphocyte / immunology*
  • Female
  • Humans
  • Male
  • Peptides / immunology*
  • Pyroglyphidae*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology

Substances

  • Allergens
  • Epitopes, T-Lymphocyte
  • Peptides