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Journal of Immunology 176, 7 (2006) 4191-200
Costimulatory receptors in a teleost fish: typical CD28, elusive CTLA4.
David Bernard 1, 2, 3, 4, Béatrice Riteau, John D Hansen 5, 6, Ruth B Phillips, Frédérique Michel 7, 8, 9, 10, 11, Pierre Boudinot 12, Abdenour Benmansour 12
(01/04/2006)

T cell activation requires both specific recognition of the peptide-MHC complex by the TCR and additional signals delivered by costimulatory receptors. We have identified rainbow trout sequences similar to CD28 (rbtCD28) and CTLA4 (rbtCTLA4). rbtCD28 and rbtCTLA4 are composed of an extracellular Ig-superfamily V domain, a transmembrane region, and a cytoplasmic tail. The presence of a conserved ligand binding site within the V domain of both molecules suggests that these receptors likely recognize the fish homologues of the B7 family. The mRNA expression pattern of rbtCD28 and rbtCTLA4 in naive trout is reminiscent to that reported in humans and mice, because rbtCTLA4 expression within trout leukocytes was quickly up-regulated following PHA stimulation and virus infection. The cytoplasmic tail of rbtCD28 possesses a typical motif that is conserved in mammalian costimulatory receptors for signaling purposes. A chimeric receptor made of the extracellular domain of human CD28 fused to the cytoplasmic tail of rbtCD28 promoted TCR-induced IL-2 production in a human T cell line, indicating that rbtCD28 is indeed a positive costimulator. The cytoplasmic tail of rbtCTLA4 lacked obvious signaling motifs and accordingly failed to signal when fused to the huCD28 extracellular domain. Interestingly, rbtCTLA4 and rbtCD28 are not positioned on the same chromosome and thus do not belong to a unique costimulatory cluster as in mammals. Finally, our results raise questions about the origin and evolution of positive and negative costimulation in vertebrate immune systems.
1 :  Service de Physique Théorique (SPhT)
CNRS : URA2306 – CEA : DSM/SPHT
2 :  Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB)
CNRS : UPR9048 – Université de Bordeaux – Ecole Nationale Supérieure de Chimie, de Biologie et de Physique
3 :  Laboratoire de Physique Théorique de l'ENS (LPTENS)
CNRS : UMR8549 – Université Pierre et Marie Curie [UPMC] - Paris VI – Ecole normale supérieure de Paris - ENS Paris
4 :  Science et Ingénierie des Matériaux et Procédés (SIMAP)
CNRS : UMR5266 – Université Joseph Fourier - Grenoble I – Institut National Polytechnique de Grenoble (INPG)
5 :  Institut Jacques Monod (IJM)
CNRS : UMR7592 – Université Paris VII - Paris Diderot
6 :  Department of Biochemistry and Molecular Biology
University of Southern Denmark
7 :  Laboratoire d'études dynamiques et structurales de la sélectivité (LEDSS)
CNRS : UMR5616 – Université Joseph Fourier - Grenoble I
8 :  Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM)
CNRS : UMR5506 – Université Montpellier II - Sciences et techniques
9 :  Centre de génétique moléculaire (CGM)
CNRS : UPR2167
10 :  Immunologie Moléculaire
Institut Pasteur de Paris – CNRS : URA1961
11 :  Signalisation des Cytokines
Institut Pasteur de Paris – CNRS : URA1961
12 :  Unité de recherche Virologie et Immunologie Moléculaires (VIM)
Institut national de la recherche agronomique (INRA) : UR0892
Sciences du Vivant/Immunologie