EXPRESSION AND CHARACTERIZATION OF HUMAN CD4 - IMMUNOGLOBULIN FUSION PROTEINS

被引:66
作者
ZETTLMEISSL, G [1 ]
GREGERSEN, JP [1 ]
DUPORT, JM [1 ]
MEHDI, S [1 ]
REINER, G [1 ]
SEED, B [1 ]
机构
[1] MASSACHUSETTS GEN HOSP, DEPT MOLEC BIOL, BOSTON, MA 02114 USA
关键词
D O I
10.1089/dna.1990.9.347
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Different chimeric antibody-like molecules consisting of the four human CD4 extracellular domains (amino acids 1–369) fused to different parts of human IgG1 and IgM heavy-chain constant regions have been created and expressed in mammalian cells. For both IgG1 and IgM fusion proteins, the best expression in COS cells was observed for molecules lacking the CH1 domain of the heavy-chain constant region. The chimeric molecules are potent inhibitors of human immunodeficiency virus (HIV) infection and HIV–mediated cytotoxicity. A CD4:IgG1 hinge fusion protein, which was analyzed in more detail, binds efficiently to HIV gpl60 and human Fc receptors and shows complement-assisted inhibition of viral propagation in culture. Half-life studies after intravenous application of the latter human fusion protein into mice and monkeys showed significant prolongation of serum survival compared to soluble CD4. An IgG2b murine homolog of the human CD4:IgG1 hinge fusion protein was prepared and evaluated in mice, where it was found to be nontoxic and to have no detectable effect on the humoral response to soluble antigen. © 1990, Mary Ann Liebert, Inc. All rights reserved.
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收藏
页码:347 / 353
页数:7
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