HLA-DP allele-specific T cell responses to beryllium account for DP-associated susceptibility to chronic beryllium disease

G Lombardi, C Germain, J Uren, M T Fiorillo, R M du Bois, W Jones-Williams, C Saltini, R Sorrentino, R Lechler

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    99 Citations (Scopus)

    Abstract

    Occupational exposure to small molecules, such as metals, is frequently associated with hypersensitivity reactions. Chronic beryllium (Be) disease (CBD) is a multisystem granulomatous disease that primarily affects the lung, and occurs in approximately 3% of individuals exposed to this element. Immunogenetic studies have demonstrated a strong association between CBD and possession of alleles of HLA-DP containing glutamic acid (Glu) at position 69 in the HLA-DP beta-chain. T cell clones were raised from three patients with CBD in whom exposure occurred 10 and 30 years previously. Of 25 Be-specific clones that were obtained, all were restricted by HLA-DP alleles with Glu at DP beta69. Furthermore, the proliferative responses of the clones were absolutely dependent upon DP beta Glu(69) in that a single amino acid substitution at this position abolished the response. As befits a disease whose pathogenesis involves a delayed type hypersensitivity response, the large majority of Be-specific clones secreted IFN-gamma (Th1) and little or no IL-4 (Th2) cytokines. This study provides insights into the molecular basis of DP2-associated susceptibility to CBD.
    Original languageEnglish
    Pages (from-to)3549 - 3555
    Number of pages7
    JournalJournal of Immunology
    Volume166
    Issue number5
    Publication statusPublished - 1 Mar 2001

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