House dust mite allergy: from T‐cell epitopes to immuno‐therapy

Abstract

Abstract. CD4+ T-lymphocytes induce and regulate allergic inflammatory responses to common environmental aeroallergens derived from Derniatophagoides spp. (house dust mite, HDM), which cause clinical symptoms in approximately 10% of the population. Definition of the molecular structure of HDM proteins combined with the ability to isolate monoclonal populations of human CD4+ T-cells representative of the 'interleukin-4 (IL-4) dominant' functional phenotype, which support immunoglobulin E (IgE) synthesis, has allowed T-cell recognition of HDM to be examined in detail. The results of these investigations demonstrated extensive heterogeneity in both the antigen and HLA class I1 restriction specificity of the HDM reactive T-cell repertoire. Furthermore, longlived clones of T-cells with oligoclonality in T-cell antigen receptor (TcR) usage, driven by chronic stimulation with HDM, have been identified in human peripheral blood. The presentation of specific peptides and superantigens under conditions that induce T-cell non-responsiveness has provided an in tiitro model for analysing the mechanisms of CD4+ T-cell targeted immunotherapy. It appears that the mechanisms underlying T-cell anergy are accompanied by a transient downregulation of TcR and CD28 and mediated by a shift in the cytokine profile from that of the 'IL-4 dominant' to the 'interferon-y (IFN-y) dominant' functional phenotype of CD4+ T-cells. In parallel, using a murine model, it has been demonstrated that administration of an immunodominant peptide via the mucosal surfaces of the respiratory and alimentary tracts may tolerize an established response to intact HDM proteins. The potential application of these models in the development of novel approaches to immunotherapy is discussed.

Analysis of Human T Cell Clones Reactive with Group V Grass Pollen Allergens

“…But all our at tempts to isolate group V reactive T cell lines from healthy persons failed throughout. Nevertheless, the presented data obtained from this panel of group V reactive TCC allow the following conclusions: The exact identification of cross-reacting (common) T cell epitopes on group V major grass pollen allergens could be very sensible due to the critical role of T cells in the regulation of allergen-specific IgE re sponses [21]. This knowledge could be utilized to test poten tial (immunodominant?)…”

“…This knowledge could be utilized to test poten tial (immunodominant?) peptides concerning immune mechanisms leading to an allergen-specific immunotolé rance fora scientifically based immunotherapy [21,22].…”

Cytokines as a Therapeutic Target for Allergic Diseases: A Complex Picture

“…In general, allergens induce T cell proliferative responses in the majority of sensitized subjects; however, the magnitude of the responses varies considerably between different individuals. Furthermore, though the magnitude of T cell proliferative responses can be higher in sensitized compared with non-sensitized individuals, this is highly variable, particularly among patients with very high titers of circulating IgE ab such as subjects with atopic dermatitis [36][37][38][39][40][41][42][43]. It has been argued that T cell responses to ubiquitous allergens such as those derived from house dust mites are universal [43].…”

Serological identification of house dust mite allergens in dogs with atopic dermatitis

“…Hypothetically, this band corresponds to Der f 2, a 129-amino acid polypeptide with a molecular weight of 14 kDa (O'Hehir et al 1993). None of the sera of the group of dogs with CAD recognized Der f 1, a major allergen for humans with a molecular weight of 24 kDa.…”