Kovacs J A, Powell F, Edman J C, Lundgren B, Martinez A, Drew B, Angus C W
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
J Biol Chem. 1993 Mar 15;268(8):6034-40.
The major surface antigen of Pneumocystis carinii, a life-threatening opportunistic pathogen in human immunodeficiency virus-infected patients, is an abundant glycoprotein that functions in host-organism interactions. A monoclonal antibody to this antigen is protective in animals, and thus this antigen is a good candidate for development as a vaccine to prevent or control P. carinii infection. We have cloned and sequenced seven related but unique genes encoding the major surface glycoprotein of rat P. carinii. Partial amino acid sequencing confirmed the identity of these genes. Based on Southern blot studies using chromosomal or restricted DNA, the major surface glycoproteins are the products of a multicopy family of genes. The predicted protein has an M(r) of approximately 123,000, is relatively rich in cysteine residues (5.5%) that are very strongly conserved, and contains a well conserved hydrophobic region at the carboxyl terminus. The presence of multiple related msg genes encoding the major surface glycoprotein of P. carinii suggests that antigenic variation is a possible mechanism for evading host defenses. Further characterization of this family of genes should allow the development of novel approaches to the control of this pathogen.
卡氏肺孢子菌是人类免疫缺陷病毒感染患者中一种危及生命的机会性病原体,其主要表面抗原是一种丰富的糖蛋白,在宿主与生物体的相互作用中发挥作用。针对该抗原的单克隆抗体在动物中具有保护作用,因此该抗原是开发预防或控制卡氏肺孢子菌感染疫苗的良好候选物。我们已经克隆并测序了七个相关但独特的基因,这些基因编码大鼠卡氏肺孢子菌的主要表面糖蛋白。部分氨基酸测序证实了这些基因的身份。基于使用染色体DNA或限制性DNA的Southern印迹研究,主要表面糖蛋白是一个多拷贝基因家族的产物。预测的蛋白质分子量约为123,000,相对富含半胱氨酸残基(5.5%),这些残基高度保守,并且在羧基末端含有一个保守的疏水区域。存在多个编码卡氏肺孢子菌主要表面糖蛋白的相关msg基因,这表明抗原变异可能是逃避宿主防御的一种机制。对该基因家族的进一步表征应该能够开发出控制这种病原体的新方法。