INHIBITION OF T-CELL AND ANTIBODY-RESPONSES TO HOUSE-DUST MITE ALLERGEN BY INHALATION OF THE DOMINANT T-CELL EPITOPE IN NAIVE AND SENSITIZED MICE

Antigen-specific CD4+ T cells play an important role in the allergic i mmune response to house dust mite (HDM) allergens in humans. The group 1 allergen of Dermatophagoides spp. is a major target antigen in both B and T cell recognition of HDM. In vitro studies have shown that the presentation of peptides to human T cells under appropriate condition s may lead to a state of specific nonresponsiveness. Therefore, to det ermine if peptides are able to modulate the function of allergen-react ive T cells in vivo, we have used a murine model of T cell recognition of the HDM allergen Der p 1. The results demonstrate that inhalation of low concentrations of peptide containing the major T cell epitope o f Der p 1 (residues 111-139), induces tolerance in naive C57BL/6J mice such that they become profoundly unresponsive to an immunogenic chall enge with the intact allergen. When restimulated in vitro with antigen , lymph node T cells isolated from tolerant mice secrete very low leve ls of interleukin 2, proliferate poorly, and are unable to provide cog nate help to stimulate specific antibody production. Furthermore, intr anasal peptide therapy was able to inhibit an ongoing immune response to the allergen in mice and this has potential implications in the dev elopment of allergen-based immunotherapy.