cDNA Sequence Diversity and Genomic Clusters of Major Surface Glycoprotein Genes of Pneumocystis carinii

Abstract

The major surface glycoprotein (MSG) of Pneumocystis carinii plays a crucial role in the pathobiology of P. carinii, which often causes fatal pneumonia in AIDS patients. The cDNAs encoding MSG antigens were cloned from a lambda gt11 expression library of rat-derived P. carinii by immunoscreening. The cloned cDNAs constituted a gene family containing approximately 70% amino acid identity between subtypes. The diversity of MSG cDNAs was high and reflected the genomic structure of MSG genes clustered in the P. carinii chromosomes. These multiple genes may account for the high-level expression of MSG that could generate potential variations in the cell surface. Moreover, the MSG sequences have significant sequence homology to tropomyosins and myosins, suggesting physical or functional association with the membrane cytoskeleton.

Adoptive transfer of lymphocytes sensitized to the major surface glycoprotein of Pneumocystis carinii confers protection in the rat.

“…Through molecular studies of rat and ferret P. carindi, it has been demonstrated that MSG represents a group of proteins encoded by multiple genes (6)(7)(8)19). Numerous unique MSG cDNAs have been identified, establishing that multiple mRNAs are transcribed within a population of organisms (6)(7)(8)(9). These data raise the possibility that antigenic variation may occur in MSG as a means of evading the host immune defenses.…”

“…With the recent progress in cloning and expressing MSG genes (6)(7)(8)(9), it should be possible to develop T cell clones, map their epitopes, and test their functional importance in vivo.…”

“…MSG, which actually represents a family of related proteins encoded by unique genes (6)(7)(8)(9), is highly immunogenic and elicits both humoral and cellular immune responses (10)(11)(12)(13)(14). It has been demonstrated that MSG is a specific T cell antigen and significantly increases the percentage of CD4 + T cells during the proliferative response (14).…”

Surfactant protein D interacts with Pneumocystis carinii and mediates organism adherence to alveolar macrophages.

“…carindi possesses several carbohydrate-rich surface proteins capable of interacting with lectins and other glycoproteins (35)(36)(37)(38)(39). In particular, P. carinji contains a major surface glycoprotein complex which has been variously termed gpA, gp 95, gpl2O, or major surface glycoprotein (40)(41)(42)(43)(44)(45). Differences in the relative molecular mass of this complex have been related to the host species from which the P. carinii are derived (35).…”

Genetic heterogeneity of Pneumocystis carinii from rats of several regions and strains

“…Contrary to this, the P. carinii from Chinese SD rats showed 85% homology rate which should be regarded as low homology because α-tubulin DNA is a gene of active translation (Wada et al, 1993). It is necessary to compare the antigenicity of the Chinese isolate.…”