Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing

Bénédicte Manoury, William F. Gregory, Rick M. Maizels, Colin Watts (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    193 Citations (Scopus)

    Abstract

    While interference with the class I MHC pathway by pathogen-encoded gene products, especially those of viruses, has been well documented, few examples of specific interference with the MHC class II pathway have been reported. Potential targets for such interference are the proteases that remove the invariant chain chaperone and generate antigenic peptides. Indeed, recent studies indicate that immature dendritic cells express cystatin C to modulate cysteine protease activity and the expression of class II MHC molecules [1]. Here, we show that Bm-CPI-2, a recently discovered cystatin homolog produced by the filarial nematode parasite Brugia malayi (W. F. Gregory et al., submitted), inhibits multiple cysteine protease activities found in the endosomes/lysosomes of human B lymphocyte lines. CPI-2 blocked the hydrolysis of synthetic substrates favored by two different families of lysosomal cysteine proteases and blocked the in vitro processing of the tetanus toxin antigen by purified lysosome fractions. Moreover, CPI-2 substantially inhibited the presentation of selected T cell epitopes from tetanus toxin by living antigen-presenting cells. Our studies provide the first example of a product from a eukaryotic parasite that can directly interfere with antigen presentation, which, in turn, may suggest how filarial parasites might inactivate the host immune response to a helminth invader.

    Original languageEnglish
    Pages (from-to)447-451
    Number of pages5
    JournalCurrent Biology
    Volume11
    Issue number6
    DOIs
    Publication statusPublished - 20 Mar 2001

    ASJC Scopus subject areas

    • General Biochemistry,Genetics and Molecular Biology
    • General Agricultural and Biological Sciences

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