HOUSE-DUST MITE ALLERGY - FROM T-CELL EPITOPES TO IMMUNOTHERAPY

CD4(+) T-Iymphocytes induce and regulate allergic inflammatory respons es to common environmental aeroallergens derived from Dermatophagoides spp. (house dust mite, HDM), which cause clinical symptoms in approxi mately 10% of the population. Definition of the molecular structure of HDM proteins combined with the ability to isolate monoclonal populati ons 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 de tail. The results of these investigations demonstrated extensive heter ogeneity in both the antigen and HLA class II restriction specificity of the HDM reactive T-cell repertoire. Furthermore, long-lived clones of T-ceIls 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 superanti gens under conditions that induce T-cell non-responsiveness has provid ed an in vitro model for analysing the mechanisms of CD4(+) T-cell tar geted immunotherapy. It appears that the mechanisms underlying T-cell anergy are accompanied by a transient downregulation of TcR and CD28 a nd mediated by a shift in the cytokine profile from that of the 'IL-4 dominant' to the 'interferon-gamma (IFN-gamma) dominant' functional ph enotype of CD4(+) T-cells. In parallel, using a murine model, it has b een demonstrated that administration of an immunodominant peptide via the mucosal surfaces of the respiratory and alimentary tracts may tole rize an established response to intact HDM proteins. The potential app lication of these models in the development of novel approaches to imm unotherapy is discussed.