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* Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104; and
Clear Springs Foods Inc., Research Division, Buhl, ID 83316
In mammals, interaction of CD28 with CD80 or CD86 molecules provides costimulatory signals for T cell activation that leads to increased IL-2 gene and protein expression by activated T cells. Thus far, CD80 and CD86 have been cloned and functionally characterized only in mammals and birds. To shed light into the evolution of CD80 and CD86, we have cloned and functionally characterized a rainbow trout (rt) molecule (rtCD80/86) that shows the highest degree of sequence conservation and phylogenetic relationship with CD80 and CD86 molecules. Moreover, its genomic organization was almost identical to that of human CD86. Rainbow trout possess one membrane-bound and two soluble CD80/86 transcripts, all of which are derived from the same rtCD80/86 gene. The membrane-bound form exhibited its highest degree of expression in lymphoid tissues, particularly on B cells. Incubation of trout leukocytes with LPS and bacteria leads to up-regulation of rtCD80/86 gene expression. Importantly, we show that trout and other teleost fish contain a single CD80/86 gene, thus suggesting that this gene may represent the ancestor from which CD80 and CD86 arose by gene duplication in more evolved species. To gain further insights into the function of rtCD80/86, we have identified and cloned trout IL-2 and have shown that recombinantly produced trout CD80/86 up-regulates the expression of IL-2 in trout blood leukocytes. Significantly, this finding indicates that the capacity to modulate IL-2 expression is a primordial function that has been conserved both in fish and mammalian CD80/CD86 molecules throughout 350 million years of evolution.
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.
1 This work was supported by U.S. Department of Agriculture Grants USDA-NRI 2006-01619 and USDA-NRI 2007-01719 (to J.O.S.) and by U.S. National Science Foundation Grant NSF-MCB-0719599 (to J.O.S.).
2 The nucleotide sequences of rainbow trout CD80/86 and IL-2 presented in this article have been submitted to GenBank under accession numbers EU927451–EU927453, FJ467621–FJ467623, and FJ607781 (for CD80/86) and FJ571512 and FJ571513 (for IL-2).
3 Y.-A.Z. and J.-i.H. contributed equally to this work.
4 Address correspondence and reprint requests to Dr. J. Oriol Sunyer, Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, 413 Rosenthal Building, 3800 Spruce Street, Philadelphia, PA 19104. E-mail address: sunyer{at}vet.upenn.edu
5 Abbreviations used in this paper: rt, rainbow trout (prefix); EST, expressed sequence tag; HKL, head kidney leukocyte; IgC, Ig constant region-like; IgV, Ig variable region-like; IPTG, isopropyl-β-D-thiogalactopyranoside; m, membrane isoform (suffix); ORF, open reading frame; PKC, protein kinase C; qPCR, quantitative real-time PCR; sl, long secretory isoform (suffix); ss, short secretory isoform (suffix); TM, transmembrane; UTR, untranslated region.
6 The online version of this article contains supplemental material.
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