THE ASSOCIATION OF HLA-DR ALLELES AND T-CELL ACTIVATION WITH ALLERGICBRONCHOPULMONARY ASPERGILLOSIS

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity l ung disease caused by the mold Aspergillus fumigatus. We previously re ported that the majority of T cell clones (TCC) isolated from three AB PA patients, and specific for a dominant Ag of A, fumigatus, Asp f 1, were IL-4-producing CD4(+) Th2 cells capable of responding to Ag in as sociation with the HLA-DR subtypes DRB11501, *1503, and *1601 for HLA -DR2, and DRB11101, *1104, and *1202 for HLA-DR5, in the present stud y we extended the previous findings to determine whether the observed restriction with the HLA-DR2/5 subtypes held importance in a larger pa tient population, Serotyping revealed that 16 of 18 ABPA patients were either HLA-DR2 HLA-DR5, or both, Compared with a normal control popul ation, the frequencies of HLA-DR2 (50 vs 22.3%) and HLA-DR5 (44,4 vs 1 9.8%) were significantly increased in these ABPA patients, Genotype an alyses of an additional 15 patients identified the same HLA-DW subtype s previously shown functional for Asp f 1 Ag presentation, The relativ e avidities of Asp f 1 peptides for the purified HLA-DR subtypes, DRB1 1501 (functional) and DRB1*1502 (nonfunctional), were examined to det ermine whether differential binding to the HLA-DR subtypes explains su ccessful Ag presentation. Similar low binding avidities were detected for both HLA-DR subtypes, indicating that the functionality cannot be simply explained by differences in binding affinities. Thus, the limit ed number and their role in Ag presentation emphasizes the possibility that the six identified HLA-DR subtypes are important in the pathophy siology of ABPA.