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J. Biol. Chem., Vol. 282, Issue 18, 13447-13455, May 4, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/18/13447    most recent M700499200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wright, J. F. Articles by Wolfman, N. M. Search for Related Content PubMed PubMed Citation Articles by Wright, J. F. Articles by Wolfman, N. M. Social Bookmarking                      What's this?

Identification of an Interleukin 17F/17A Heterodimer in Activated Human CD4+ T Cells^*

Jill F. Wright¹, Yongjing Guo, Amira Quazi, Deborah P. Luxenberg, Frann Bennett, John F. Ross, Yongchang Qiu, Matthew J. Whitters, Kathleen N. Tomkinson, Kyri Dunussi-Joannopoulos, Beatriz M. Carreno², Mary Collins, and Neil M. Wolfman

From the Departments of Inflammation and Biological Technologies, Wyeth Research, Cambridge, Massachusetts 02140

IL-17F and IL-17A are members of the IL-17 pro-inflammatory cytokine family. IL-17A has been implicated in the pathogenesis of autoimmune diseases. IL-17F is a disulfide-linked dimer that contains a cysteine-knot motif. We hypothesized that IL-17F and IL-17A could form a heterodimer due to their sequence homology and overlapping pattern of expression. We evaluated the structure of recombinant IL-17F and IL-17A proteins, as well as that of natural IL-17F and IL-17A derived from activated human CD4+ T cells, by enzyme-linked immunosorbent assay, immunoprecipitation followed by Western blotting, and mass spectrometry. We find that both IL-17F and IL-17A can form both homodimeric and heterodimeric proteins when expressed in a recombinant system, and that all forms of the recombinant proteins have in vitro functional activity. Furthermore, we find that in addition to the homodimers of IL-17F and IL-17A, activated human CD4+ T cells also produce the IL-17F/IL-17A heterodimer. These data suggest that the IL-17F/IL-17A heterodimer may contribute to the T cell-mediated immune responses.

Received for publication, January 18, 2007 , and in revised form, February 20, 2007.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Current address: Washington University School of Medicine, Division of Oncology, 660 South Euclid Ave., Campus Box 8007, St. Louis, MO, 63110.

² To whom correspondence should be addressed: 200 Cambridge Park Dr., Cambridge, MA 02140. Tel.: 617-665-5324; Fax: 617-665-5386; E-mail: jwright{at}wyeth.com.

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