Identification of a 65-kDa mannoprotein as a main target of human cell-mediated immune response to Candida albicans

To identify molecular targets of anticandidal cell-mediated immunity (CMI) in humans, a highly immunogenic mannoprotein fraction (MP-F2) of Candida albicans was studied. SDS-PAGE and gel-permeation chromatography separated MP-F2 into polydisperse mannoproteins of > 200-31.5 kDa. However, only a 65-kDa constituent specifically induced proliferation of human peripheral blood mononuclear cells (PBMC). Lymphoproliferation was accompanied by production of interleukin (IL)-1 beta, interferon-gamma, and IL-6 but not IL-4. MP-F2- and MP-65-induced PBMC proliferation was inhibited by an antagonist anti-T cell receptor antibody. Neither the purified protein derivative of Mycobacterium tuberculosis nor MP-65 activated naive lymphocytes from umbilical cord blood, although these cells proliferated extensively in response to both phytohemagglutinin and IL-2. These data strongly suggest that MP-65 is an immunodominant mannoprotein antigen that is ordinarily expressed as a target of anti-Candida CMI in healthy humans.