Allergen and Epitope Targets of Mouse-Specific T Cell Responses in Allergy and Asthma

Front Immunol. 2018 Feb 13;9:235. doi: 10.3389/fimmu.2018.00235. eCollection 2018.

Abstract

Mouse allergy has become increasingly common, mainly affecting laboratory workers and inner-city households. To date, only one major allergen, namely Mus m 1, has been described. We sought to identify T cell targets in mouse allergic patients. PBMC from allergic donors were expanded with either murine urine or epithelial extract and subsequently screened for cytokine production (IL-5 and IFNγ) in response to overlapping peptides spanning the entire Mus m 1 sequence, peptides from various Mus m 1 isoforms [major urinary proteins (MUPs)], peptides from mouse orthologs of known allergens from other mammalian species and peptides from proteins identified by immunoproteomic analysis of IgE/IgG immunoblots of mouse urine and epithelial extracts. This approach let to the identification of 106 non-redundant T cell epitopes derived from 35 antigens. Three major T cell-activating regions were defined in Mus m 1 alone. Moreover, our data show that immunodominant epitopes were largely shared between Mus m 1 and other MUPs even from different species, suggesting that sequence conservation in different allergens is a determinant for immunodominance. We further identified several novel mouse T cell antigens based on their homology to known mammalian allergens. Analysis of cohort-specific T cell responses revealed that rhinitis and asthmatic patients recognized different epitope repertoires. Epitopes defined herein can be formulated into an epitope "megapool" used to diagnose mouse allergy and study mouse-specific T cell responses directly ex vivo. This analysis of T cell epitopes provides a good basis for future studies to increase our understanding of the immunopathology associated with MO-allergy and asthma.

Keywords: Mus m 1; T cell epitope; allergic rhinitis; asthma; mouse allergy.

Publication types

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

MeSH terms

  • Adult
  • Allergens / immunology
  • Animal Technicians
  • Animals
  • Animals, Laboratory / immunology
  • Asthma / blood
  • Asthma / immunology*
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Humans
  • Immunodominant Epitopes / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukin-5 / immunology
  • Interleukin-5 / metabolism
  • Male
  • Mice / immunology*
  • Middle Aged
  • Occupational Diseases / blood
  • Occupational Diseases / immunology*
  • Proteins / immunology
  • Rhinitis, Allergic / blood
  • Rhinitis, Allergic / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Allergens
  • Epitopes, T-Lymphocyte
  • IFNG protein, human
  • IL5 protein, human
  • Immunodominant Epitopes
  • Interleukin-5
  • Proteins
  • major urinary proteins
  • Interferon-gamma