Identification of an interleukin 17F/17A heterodimer in activated human CD4+ T cells.
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.
Wright
Jill F
JF
Department of Inflammation, Wyeth Research, Cambridge, Massachusetts 02140, USA. jwright@wyeth.com
Guo
Yongjing
Y
Quazi
Amira
A
Luxenberg
Deborah P
DP
Bennett
Frann
F
Ross
John F
JF
Qiu
Yongchang
Y
Whitters
Matthew J
MJ
Tomkinson
Kathleen N
KN
Dunussi-Joannopoulos
Kyri
K
Carreno
Beatriz M
BM
Collins
Mary
M
Wolfman
Neil M
NM
D020816:Amino Acid Motifs; D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003545:Cysteine / Q000235:genetics / Q000276:immunology; D019281:Dimerization; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*
C508717:IL17A protein, human; C440021:IL17F protein, human; D020381:Interleukin-17; D003545:Cysteine