AN IMMUNOGENETIC ANALYSIS OF THE T-CELL RECOGNITION OF THE MAJOR HOUSE-DUST MITE ALLERGEN DER-P-2 - IDENTIFICATION OF HIGH-RESPONDER AND LOW-RESPONDER HLA-DQ ALLELES AND LOCALIZATION OF T-CELL EPITOPES

Cellular reactivity to Der p 2, a major allergen of the house dust mit e (HDM) Dermatophagoides pteronyssinus, was studied in a group of 41 s ymptomatic HDM sensitive patients, using fresh peripheral blood mononu clear cells (PBMC) and assays of proliferation. Sixty per cent of the patients responded to Der p 2, with reactivities being greater in pati ents with asthma as one of their clinical manifestations and also in t hose who had skin-test reactivity to a number of allergens. KLA-DR and -DQ serotyping was undertaken in 39 of the patients and the magnitude of T-cell proliferative responses to Der p 2 were found to be positiv ely associated with DQ7 and negatively associated with DQ2. T-cell det erminants within the Der p 2 molecule were identified by assays using a series of overlapping peptides (15- to 19-mers) spanning the entire protein. Fifty-nine per cent of the 41 HDM-sensitive patients responde d to one or more of the peptides. All of the peptides were antigenic f or at least one of the individuals, indicating the heterogeneity of th e human repertoire reactive with Der p 2. There was a substantial vari ability in the number and location of epitopes recognized by T cells f rom the different allergic patients, the mean number per patient being 2.3 +/- 1.3 (SD). The most frequently recognized peptide was that spa nning residues 111-129, being stimulatory in 66.7%, the other peptides were each recognized by between 8 to 25% of individuals. There was no correlation between the epitope recognized and the presence of partic ular HLA-DQ antigens.