Superantigen-like effects of a Candida albicans polypeptide

The amino terminal sequence of the Candida albicans cell wall protein Int1 exhibited partial identity with the major histocompatibility complex (MHC) class II binding site of the Mycoplasma arthritidis superantigen MAM. Int1-positive C. albicans blastospores activated human T lymphocytes and expanded Vβ subsets 2, 3, and/or 14; Int1-negative strains were inactive. Release of interferon-γ (IFN-γ) but not of tumor necrosis factor-α or interleukin-6 was Int1 dependent; interleukin-4 and interleukin-10 were not detected. T lymphocyte activation, Vβ expansion, and IFN-γ release were associated with a soluble polypeptide that encompassed the first 263 amino acids of Int1 (Pep₂₆₃). Monoclonal antibody 163.5, which recognizes an Int1 epitope that overlaps the region of identity with MAM, significantly inhibited these activities when triggered by Int1-positive blastospores or Pep₂₆₃ but not by staphylococcal enterotoxin B. Histidine ₂₆₃ was required. Pep₂₆₃ bound to T lymphocytes and MHC class II and was detected in the urine of a patient with C. albicans fungemia. These studies identify a candidal protein that displays superantigen-like activities.