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The Journal of Immunology, 2004, 172: 2352-2359.
Copyright © 2004 by The American Association of Immunologists

Molecular Characterization of Human 4Ig-B7-H3, a Member of the B7 Family with Four Ig-Like Domains1

Peter Steinberger2,*,{dagger}, Otto Majdic*, Sophia V. Derdak*,{ddagger}, Katharina Pfistershammer*, Stefanie Kirchberger*, Christoph Klauser*,{dagger}, Gerhard Zlabinger*, Winfried F. Pickl*,{ddagger}, Johannes Stöckl* and Walter Knapp*

* Institute of Immunology, University of Vienna Medical School, Vienna, Austria; {dagger} Competence Center "Bio-Molecular Therapeutics", Vienna, Austria; and {ddagger} CeMM Center for Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria

In an effort to characterize molecules with immunoregulatory potential, we raised mAbs to human dendritic cells. We selected an Ab that recognizes a molecule that is induced on monocytes differentiated in vitro toward dendritic cells. Retroviral expression cloning identified this molecule as B7-H3, a member of the B7 family described recently. In contrast to an earlier report, in which B7-H3 was described as a molecule consisting of two Ig-like domains, our cDNA encoded a type I membrane protein with four Ig-like domains, and the molecule identified by us was therefore named 4Ig-B7-H3. mRNA analysis as well as Western blotting experiments performed by us did not reveal evidence for a small B7-H3. B7-H3 is not expressed on peripheral blood lymphocytes, monocytes, or granulocytes. Upon in vitro stimulation, the expression of B7-H3 is induced on T cells, B cells, and NK cells. A number of different approaches were used to investigate the function of human B7-H3. In contrast to an earlier report, our data do not support a costimulatory role of B7-H3 in anti-CD3-mediated activation of the TCR-complex resulting in T cell proliferation and IFN-{gamma} production.




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