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Isoforms of the class II transactivator protein. (Articolo in rivista)

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Isoforms of the class II transactivator protein. (Articolo in rivista) (literal)

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Barbieri G 1, Deffrennes V 1, Prod'homme T 1, Vedrenne J 1, Baton F 1, Cortes C 3, Fischer A 2, Bono MR 3, Lisowska-Grospierre B 2, Charron D 1, Alcaide-Loridan C 1. (2002)
Isoforms of the class II transactivator protein.
in International immunology (Print); Oxford University Press, Oxford (Regno Unito)
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Barbieri G 1, Deffrennes V 1, Prod'homme T 1, Vedrenne J 1, Baton F 1, Cortes C 3, Fischer A 2, Bono MR 3, Lisowska-Grospierre B 2, Charron D 1, Alcaide-Loridan C 1. (literal)

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Within this context, one possibility is that the abnormal and constitutive expression of both F- and B-CIITA could have a role in the bad prognosis associated with the constitutive expression of MHC class II molecules in primary melanoma, maybe activating the expression of proteins involved in tumour invasiveness or immune escape. These data therefore might give further indications about the putative involvement of the CIITA expression abnormalities observed in various tumour cell types. (literal)

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Even though CIITA is an essential component of MHC class II regulation, little is known about this protein in its native form. Indeed, due to its extremely low expression level, most studies have been performed in transfected cells over-expressing recombinant forms of the protein. In this report, our goal was to obtain the first visualisation the endogenous CIITA protein and to analyse its expression in response to IFN gamma. In addition our aim was to precisely dissect the cascade of events leading to the cell-surface expression of the HLA-D molecules towards the establishment of a complete view of the respective kinetics of CIITA and HLA-D transcripts and proteins in response to the cytokine. We have also analysed the pattern of the native CIITA protein expression in various MHC class II-constitutive expressing melanoma cell lines and shown that both B lymphocytes (B-CIITA) and fibroblast (F-CIITA) specific CIITA isoforms are expressed. (literal)

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1 INSERM U396, Centre de Recherches Biomédicales des Cordeliers and Laboratoire d'Immunologie et d'Histocompatibilité, APHP, Hôpital St Louis, 75270 Paris, France; 2 INSERM U429, Hôpital Necker Enfants-Malades, 75015 Paris, France; 3 Departamento de Biologia, Facultad de Ciencias, Universidad de Chile, Santiago, Chile (literal)

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Abstract

The class II transactivator (CIITA) controls both the constitutive and IFN-gamma inducible expression of HLA-D genes. In addition, through the squelching of another transactivator CREB-binding protein, CIITA was more recently shown to have a wider cellular function, including cell cycle control or cellular response to IFN-gamma and IL-4. However, due to its low expression level, its analysis mainly relies on the study of recombinant overexpressed forms of the protein. We report here the analysis of native CIITA in various cell types. We first show the precise timing of CIITA protein expression in a fibroblast cell line in response to IFN-gamma. This expression is observed 2 h after the cytokine addition with a peak of expression ranging from 16 to 24 h. We next show the existence of two major isoforms of the CIITA protein differentially expressed in fibroblast, B lymphocyte or melanoma cell lines. We present the first demonstration that these isoforms originate from alternative translation initiation codons. We finally show that CIITA isoforms translocate to the nucleus with an apparently similar efficiency. Our data therefore demonstrate the existence of CIITA isoforms whose respective ratio depends on the cell type examined. However, we present evidence for a modulation of this ratio in a melanoma cell line with an abnormal constitutive expression of MHC class II molecules. (literal)

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