Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening.
The previously cloned human interferon alpha/beta (Hu-IFN-alpha/beta; Type I interferon) receptor cDNA appears to be only one component of a receptor complex since expression of the cDNA in mouse cells confers sensitivity only to Hu-IFN-alpha B2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of Hu-IFN-alpha A, Hu-IFN-alpha B2, Hu-IFN-omega, and Hu-IFN-beta. Here we report that a yeast artificial chromosome (YAC) containing a segment of human chromosome 21 introduced into Chinese hamster ovary (CHO) cells confers upon these cells a greatly enhanced response to Hu-IFN-alpha A and Hu-IFN-alpha B2 as well as an increased response to Hu-IFN-omega, Hu-IFN-alpha A/D(Bgl), andd Hu-IFN-beta. These responses were measured by induction of class I MHC antigens and by protection against encephalomyocarditis virus and vesicular stomatitis virus. Furthermore, these cells exhibit specific high affinity binding of Hu-IFN-alpha A and Hu-IFN-alpha B2, Hu-IFN-beta, and Hu-IFN-omega. The results indicate that all the genes necessary to reconstitute a biologically active Type I human IFN receptor complex are located within the human DNA insert of this YAC clone.
Soh
J
J
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway 08854-5635.
Mariano
T M
TM
Lim
J K
JK
Izotova
L
L
Mirochnitchenko
O
O
Schwartz
B
B
Langer
J A
JA
Pestka
S
S
D000818:Animals; D016466:CHO Cells; D018244:Chromosomes, Artificial, Yeast; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004686:Encephalomyocarditis virus / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D016898:Interferon-alpha / Q000276:immunology / Q000378:metabolism; D016899:Interferon-beta / Q000276:immunology / Q000378:metabolism; D017471:Receptors, Interferon / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D016899:Interferon-beta