A Major Allergen of Lymphatic Filarial Nematodes Is a Parasite Homolog of the γ-Glutamyl Transpeptidase

Autor: Niklaus Weiss, Edgar Lobos, Regina Zahn, Thomas B. Nutman
Rok vydání: 1996
Předmět:
Zdroj: Molecular Medicine. 2:712-724
ISSN: 1528-3658
1076-1551
DOI: 10.1007/bf03401655
Popis: Bm2325, a major IgE-inducing antigen of the filarial parasite Brugia malayi has been implicated in the pathology of tropical pulmonary eosinophilia (TPE), a pulmonary syndrome thought to result from hypersensitivity to microfilariae. Affinity-purified IgE to Bm2325 from patients with TPE was used to identify a complementary DNA (cDNA) from a B. malayi expression library. Sequence analysis of the cDNA revealed a hitherto unknown parasite protein. Immunoblotting of the recombinant filarial protein using sera of patients with TPE determined its IgE-binding capacity. Reactivity to human lung epithelial cell proteins was analyzed using murine anti-Bm2325 antibodies and serum from patients with TPE. The predicted protein is a homolog of the entire precursor of the γ-glutamyl transpeptidase (γ-GT), a key enzyme in the synthesis and degradation of glutathione. The filarial precursor encodes both the heavy (H) and the light (L) chain subunits and shares structural similarities with the mammalian enzymes. The Bm2325 allergen was identified as the homolog of the enzyme light chain subunit. Murine antibodies against the recombinant parasite γ-GT cross-reacted with the human enzyme present in human airway epithelial cells, and human γ-GT is a target of antibodies present in the serum of patients with TPE. Molecular mimicry between the parasite γ-GT homolog and the host membrane-bound γ-GT present in lung epithelial cells likely contributes to the pathogenesis observed in tropical pulmonary eosinophilia.
Databáze: OpenAIRE
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