T-CELL SUBSETS, EPITOPE MAPPING, AND HLA-RESTRICTION IN PATIENTS WITHALLERGIC BRONCHOPULMONARY ASPERGILLOSIS

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity l ung disease characterized by Aspergillus fumigatus (Af) colonization, IgE and IgG anti-Af antibodies, pulmonary infiltrates, bronchiectasis, and pulmonary fibrosis, Little is known regarding T cell responses an d their role in the pathogenesis of ABPA, To examine T cell reactivity to Af antigens, T cell clones (TCC) specific to the Asp fl antigen, a n 18-kD protein of Af, were established from the peripheral blood of t hree ABPA patients. The majority of TCC isolated from ABPA patients, a nd specific for the Asp f 1 allergen of Af, are IL-4 producing CD4+ ce lls of the Th2 phenotype, Further analysis in this study revealed that the majority of TCC reacted to mainly two epitopes of Asp f 1, while the remaining TCC reacted to three additional ''minor'' epitopes. Bloc king studies using monoclonal antibodies specific for class ZI HLA-D r egion gene products showed that most TCC, 19/21, were restricted by HL A-DR molecules, and the remaining two clones by HLA-DP molecules. The use of a panel of HLA-matched and mismatched EBV-transformed B cells a s antigen presenting cells revealed that the HLA-DR restriction was me diated exclusively by either the HLA-DR2 or HLA-DRS alleles, Genotypin g of DRB1 gene products showed that class II presentation for most clo nes was not restricted to a single allele, representing DRB1 gene prod ucts of either HLA-DR2 or DR5. These studies offer insight into the ce llular and molecular determinants which contribute to the immunopathop hysiology of ABPA, (J. Clin. Invest. 1995. 97:2324-2331.)