Antigenic structure of Coccidioides immitis

Abstract

Coccidioides immitis is a unique fungal pathogen, characterized by a saprobic mycelial phase that gives rise to infectious arthroconidia which in host tissue, convert into a morphologically distinct spherule-endospore phase. This multiphasic cycle presents a formidable challenge to the host. The cell wall of C. immitis is a major reservoir of immunoreactive antigens and thus figures prominently in host-parasite interaction in this disease. Extracts of cell walls have yielded antigens reactive with the TP and CF antibodies, antigens that elicit in vivo and in vitro T-cell responses, and antigens that augment or suppress host response. By using techniques of 2D-IEP and Western blotting, investigators have provided evidence that the TP antigen has a predominant polysaccharide composition, with a molecular weight range of 130-330 kD. This antigen may have tolerogenic activity, as suggested by the induction of IgM antibody early during the disease, which then wanes and is followed by a modest or nondemonstrable IgG antibody response. In contrast, the CF antigen is highly immunogenic, inducing IgG levels within 1 to 3 months of clinical illness, which then persist throughout the course of disease. Compositional analyses of the CF antigen indicate that this heat-labile precipitinogen is a glycolipoprotein complex with a molecular weight range of 43-48 kD. The skin test active component(s) of C. immitis has not been purified, but preliminary evidence suggests that it may be a polymeric antigen designated as Ag2. This polymeric antigen is susceptible to enzymatic treatment with mannosidase and protease, indicating a mannoprotein composition, although other constituents may be present as well. Despite differences in the chemical composition of Ag2 and the TP antigen, these two components coelute on molecular sieve, ion-exchange, and lectin affinity columns and both antigens are solubilized from cell walls with alkali. These similar chromatographic profiles suggest that Ag2 and the TP antigen are intimately associated and perhaps present as a complex. Comparative analyses of morphological forms of C. immitis have provided evidence that extracts from spherules are more potent than those from the mycelial phase in eliciting immune responses. These differences may, however, be attributed to quantitative rather than qualitative differences in the antigenic composition of these cell types. In summary, many advances have been made in the isolation and characterization of antigens from this pathogenic fungus. However, additional work is required to fully delineate their production and expression during the morphogenetic phases of C. immitis and to assess their role in the pathophysiology of coccidioidomycosis.