Different Bla-g T cell antigens dominate responses in asthma versus rhinitis subjects

Clin Exp Allergy. 2015 Dec;45(12):1856-67. doi: 10.1111/cea.12643.

Abstract

Background and objective: The allergenicity of several German cockroach (Bla-g) antigens at the level of IgE responses is well established. However, less is known about the specificity of CD4+ TH responses, and whether differences exist in associated magnitude or cytokine profiles as a function of disease severity.

Methods: Proteomic and transcriptomic techniques were used to identify novel antigens recognized by allergen-specific T cells. To characterize different TH functionalities of allergen-specific T cells, ELISPOT assays with sets of overlapping peptides covering the sequences of known allergens and novel antigens were employed to measure release of IL-5, IFNγ, IL-10, IL-17 and IL-21.

Results: Using these techniques, we characterized TH responses in a cohort of adult Bla-g-sensitized subjects, either with (n = 55) or without (n = 17) asthma, and nonsensitized controls (n = 20). T cell responses were detected for ten known Bla-g allergens and an additional ten novel Bla-g antigens, representing in total a 5-fold increase in the number of antigens demonstrated to be targeted by allergen-specific T cells. Responses of sensitized individuals regardless of asthma status were predominantly TH 2, but higher in patients with diagnosed asthma. In asthmatic subjects, Bla-g 5, 9 and 11 were immunodominant, while, in contrast, nonasthmatic-sensitized subjects responded mostly to Bla-g 5 and 4 and the novel antigen NBGA5.

Conclusions: Asthmatic and nonasthmatic cockroach-sensitized individuals exhibit similar TH 2-polarized responses. Compared with nonasthmatics, however, asthmatic individuals have responses of higher magnitude and different allergen specificity.

Keywords: CD4+ T cell; asthma; cockroach allergy; epitope.

Publication types

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

MeSH terms

  • Adult
  • Allergens / immunology*
  • Animals
  • Antigen Presentation
  • Asthma / immunology*
  • Asthma / metabolism
  • Blattellidae / genetics
  • Blattellidae / immunology*
  • Blattellidae / metabolism
  • Case-Control Studies
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / chemistry
  • Epitopes, T-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / metabolism
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Immunization
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Peptides / chemistry
  • Peptides / immunology
  • Peptides / metabolism
  • Rhinitis / immunology*
  • Rhinitis / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Young Adult

Substances

  • Allergens
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Immunodominant Epitopes
  • Peptides