Hiromatsu Kenji, Dascher Christopher C, Sugita Masahiko, Gingrich-Baker Cindy, Behar Samuel M, LeClair Kenneth P, Brenner Michael B, Porcelli Steven A
Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
Immunology. 2002 Jun;106(2):159-72. doi: 10.1046/j.1365-2567.2002.01422.x.
CD1 molecules are cell-surface glycoproteins with strong structural similarities to major histocompatibility complex (MHC) class I molecules, and studies in humans and mice have demonstrated that CD1 proteins perform the unique role of presenting lipid antigens to T lymphocytes. Our previous studies have shown that guinea-pigs, unlike the muroid rodents, have an extended family of group 1 CD1 genes. In the current study, we raised monoclonal anibodies (mAbs) against guinea-pig CD1 proteins and generated transfected cell lines expressing individual members of the guinea-pig CD1 family. Our results indicated that multiple members of the guinea-pig CD1 family, including members that are homologous to the human CD1b and CD1c proteins, are expressed at the protein level in transfected cells and in specialized antigen-presenting cells such as monocyte-derived dendritic cells. In addition, CD1 proteins, especially guinea-pig CD1b3, were expressed on a large number of B cells in the guinea-pig, and CD1 expression appeared to be regulated by B-cell maturation or differentiation. Interestingly, three different patterns of intracellular localization were observed for the various guinea-pig CD1 isoforms, a finding that is reminiscent of the distinct patterns of intracellular localization that have been previously demonstrated for human CD1a, CD1b and CD1c. Taken together, these results provide further evidence for substantial similarities between the guinea-pig and human CD1 systems, thus supporting the possibility that the guinea-pig may offer significant advantages as an animal model for the study of the in vivo role of CD1 proteins in infectious and autoimmune diseases.
CD1分子是细胞表面糖蛋白,与主要组织相容性复合体(MHC)I类分子在结构上有很强的相似性。对人类和小鼠的研究表明,CD1蛋白在向T淋巴细胞呈递脂质抗原方面发挥着独特作用。我们之前的研究表明,与鼠类啮齿动物不同,豚鼠拥有一个扩展的1类CD1基因家族。在本研究中,我们制备了针对豚鼠CD1蛋白的单克隆抗体(mAb),并建立了表达豚鼠CD1家族各个成员的转染细胞系。我们的结果表明,豚鼠CD1家族的多个成员,包括与人类CD1b和CD1c蛋白同源的成员,在转染细胞和诸如单核细胞衍生树突状细胞等特殊抗原呈递细胞中以蛋白质水平表达。此外,CD1蛋白,尤其是豚鼠CD1b3,在豚鼠的大量B细胞上表达,并且CD1的表达似乎受B细胞成熟或分化的调节。有趣的是,观察到各种豚鼠CD1亚型有三种不同的细胞内定位模式,这一发现让人想起先前在人类CD1a、CD1b和CD1c中所证明的不同细胞内定位模式。综上所述,这些结果为豚鼠和人类CD1系统之间的实质性相似性提供了进一步证据,从而支持豚鼠作为研究CD1蛋白在感染性和自身免疫性疾病中体内作用的动物模型可能具有显著优势的可能性。