Molecular cloning and characterization of murine ICOS and identification of B7h as ICOS ligand

Abstract

Human ICOS (huICOS) is a T cell-specific molecule structurally related to CD28 and CTLA-4 with potent co-stimulatory activities on T cell proliferation, cytokine induction and T cell help for B cells. We have now cloned and characterized murine ICOS (muICOS). muICOS mRNA of 1.5 kb and 3.3 kb encodes a protein with a deduced molecular mass of 20.3 kDa, which is 71.7% identical to huICOS. On the cell surface, muICOS is expressed as a disulfide-linked, glycosylated homodimer of 47-57 kDa, with subunits of approximately 26 kDa. With a panel of monoclonal antibodies we have determined the expression of muICOS in vitro and in vivo. Following activation of splenic T cells via CD3, muICOS became detectable at 12 h and reached a maximum of expression at around 48 h, thus exhibiting expression kinetics similar to huICOS. In vivo, muICOS was found to be substantially expressed in the thymic medulla and in the germinal centers and T cell zones of lymph nodes and Peyer's patches. Non-lymphoid tissue was ICOS negative. The muICOS gene was mapped to a region of chromosome 1 also harboring the CD28 and CTLA-4 genes. Using recombinant chimeric muICOS-Ig we determined that B7h, a recently cloned B7-like molecule, is a ligand for muICOS.