University of Medicine and Dentistry of New Jersey

Serguei V Kotenko

Sidney Pestka

Robert J Donnelly

Stuart Emanuel

Barbara Schwartz

Thomas M Mariano

Jaemog Soh

Jeffry R Cook

This invention relates (a) to a 540 kb YAC which encodes the necessary species-specific factor(s) and is able to substitute for human Chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens; (b) to the construction of a plasmid to integrate the selective marker for antibiotic G418 resistance into YACs and to delete some of the human DNA fragments from YACs in order to facilitate the manipulation of human genomic DNA in yeast artificial chromosome (YAC) clones; (c) to two fragmentation vectors, pSE1 and pSE2, which contain a neomycin resistance and URA3 gene, developed for targeting yeast artificial chromosomes (YACs) containing human genomic DNA; (d) to a chromosomal fragmentation procedure employed to produce a deletion set of yeast artificial chromosomes (YACs) from a parental YAC (GART D142H8) known to map to Chromosome 21q and to encode the human interferon-gamma receptor (Hu-IFN-gamma R) accessory factor gene as well as the phosphoribosylglycinamide formyltranisferase (GART) gene; and (e) to the isolation of cDNA clones that encode the necessary species-specific factor and that are able to substitute for human Chromosome 21 to reconstitute the Hu-IFN-gamma receptor-mediated induction of class I HLA antigens.

Accessory factory function for interferon gamma and its receptor

The present invention relates to the identification of intracellular signal transduction function for a putative cytokine receptor subunit. In particular, the invention relates to the identification of the signal transduction protein for the interleukin (IL)-10 receptor. Accordingly, the present invention relates to preparing recombinant cells that express the IL-10 receptor and the newly identified IL-10 signal transduction protein, e.g., for use in screening libraries of compounds for IL-10 agonists and antagonists; to restoring IL-10 function to cells in vivo, e.g., via gene therapy; and in addition to chimeric proteins comprising this signal transduction protein to agonize IL-10 activity. In specific examples, cells transfected with both the first chain of the IL-10R and the presently identified second chain, termed herein CRFB4, were able to transduce a signal in response to contact with IL-10.

Cells expressing IL-10 receptor and the CRFB4 gene product, an IL-10

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Highland Park, NJ, United States of America

Serguei V Kotenko