Nature Biotechnology
21, 302 - 307 (2003)
Published online: 24 February 2003; | doi:10.1038/nbt797
TIP, a T-cell factor identified using high-throughput screening
increases survival in a graft-versus-host disease modelMichele Fiscella1, James W. Perry2, Baiqin Teng1, Michael Bloom2, Chen Zhang2, Kam Leung3, Laurie Pukac3, Kimberly Florence3, Alice Concepcion3, Binjun Liu3, Ying Meng3, Cecil Chen3, Erika Cochrane Elgin2, Palanisamy Kanakaraj2, Thomas E. Kaufmann2, Joelle Porter1, Ricardo Cibotti2, Yun Mei2, Joe Zhou4, Guoxian Chen4, Viktor Roschke5, George Komatsoulis6, Brian Mansfield1, Steve Ruben1, Indra Sanyal3
& Thi-Sau Migone21
Department of Preclinical Discovery, Human Genome
Sciences, Inc., Rockville, MD 20850. 2
Department of Preclinical Development, Human
Genome Sciences, Inc., Rockville, MD
20850. 3
Department of Lead Development and
Characterization, Human Genome Sciences, Inc., Rockville,
MD 20850. 4
Department of Protein Development, Human Genome
Sciences, Inc., Rockville, MD 20850. 5
Department of Antibody Development, Human Genome
Sciences, Inc., Rockville, MD 20850. 6
Department of Information Technology, Human Genome
Sciences, Inc., Rockville, MD 20850.
Correspondence should be addressed to Thi-Sau Migone T.Migone@genesis.co.nzA coordinated effort combining bioinformatic tools with
high-throughput cell-based screening assays was implemented to identify novel
factors involved in T-cell biology. We generated a unique library of cDNAs
encoding predicted secreted and transmembrane domain−containing proteins
generated by analyzing the Human Genome Sciences cDNA database with a
combination of two algorithms that predict signal peptides. Supernatants from
mammalian cells transiently transfected with this library were incubated with
primary T cells and T-cell lines in several high-throughput assays. Here we
describe the discovery of a T cell factor, TIP (T cell immunomodulatory
protein), which does not show any homology to proteins with known function.
Treatment of primary human and murine T cells with TIP in vitro resulted
in the secretion of IFN- , TNF- , and IL-10, whereas in vivo
TIP had a protective effect in a mouse acute graft-versus-host disease
(GVHD) model. Therefore, combining functional genomics with high-throughput
cell-based screening is a valuable and efficient approach to identifying
immunomodulatory activities for novel proteins.
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