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Title: A CD4 homologue in sea bass (Dicentrarchus labrax): Molecular characterization and structural analysis
Authors: Buonocore, Francesco
Randelli, Elisa
Casani, Daniela
Guerra, Laura
Picchietti, Simona
Costantini, Susan
Facchiano, Angelo M.
Zou, Jun
Secombes, Chris J.
Scapigliati, Giuseppe
Keywords: Fish Immunology;Molecular Biology;CD4;Dicentrarchus labrax
Issue Date: 2011
Publisher: Elsevier
Source: Buonocore, F. et al. 2008. A CD4 homologue in sea bass (Dicentrarchus labrax): Molecular characterization and structural analysis. "Molecular Immunology" 45 (11): 3168-3177
CD4 is a transmembrane glycoprotein fundamental for cell-mediated immunity. Its action as a T cell coreceptor
increases the avidity of association between a T cell and an antigen-presenting cell by interacting
with portions of the complex between MHC class II and TR molecules. In this paper we report the cDNA
cloning, expression and structural analysis of a CD4 homologue from sea bass (Dicentrarchus labrax). The
sea bass CD4 cDNA consists of 2071 bp that translates in one reading frame to give the entire molecule
containing 480 amino acids. The analysis of the sequence shows the presence of four putative Ig-like
domains and that some fundamental structural features, like a disulphide bond in domain D2 and the CXC
signalling motif in the cytoplasmic tail, are conserved from sea bass to mammals. Real-time PCR analysis
showed that very high levels of CD4 mRNA transcripts are present in thymus, followed by gut and gills. In
vitro stimulation of head kidney leukocytes with LPS and PHA-L gave an increase of CD4 mRNA levels after
4 h and a decrease after 24 h. Homology modelling has been applied to create a 3D model of sea bass CD4
and to investigate its interaction with sea bass MHC-II. The analysis of the 3D complex between sea bass
CD4 and sea bass MHC-II suggests that the absence of a disulfide bond in the CD4 D1 domain could make
this molecule more flexible, inducing a different conformation and affecting the binding and the way of
interaction between CD4 and MHC-II. Our results will add new insights into the sea bass T cell immune
responses and will help in the identification of T cell subsets in teleost fishes to better understand the
evolution of cell-mediated immunity from fish to mammals.
L'articolo è disponibile sul sito dell'editore
ISSN: 0161-5890
DOI: 10.1016/j.molimm.2008.02.024
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