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Identification of Three Alternatively Spliced Variants of Human CD28 mRNA

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Abstract

CD28, expressed by T cells, plays a central role in providing costimulatory signals to T cells. Thecd28gene is organized into 4 exons. An alternatively spliced CD28 mRNA lacking most of the exon 2 has been previously evidenced. We report here that non stimulated human T cells express three additional alternatively spliced variants of CD28 mRNA (CD28a-c) in. The CD28a variant, expressed at similar levels to that of the full length CD28 mRNA encoding for the membrane form, lacks exon 3. This deletion introduces (i) a frame shift resulting in the addition of two extra amino acids and a premature stop codon and, (ii) induces the loss of the transmembrane region, suggesting that it could encodes for a soluble monomeric molecule which conserves the binding sites of CD28. The CD28b and CD28c variants, expressed at a low level compared with CD28a, are generated by deletion of most of the 3′ end of exon 2 plus exon 3 and exon 2 plus exon 3, respectively. Activated T cells express only the membrane CD28 mRNA. These results suggest that resting human T cells may constitutively express both membrane and soluble CD28 which can differentially regulate the outcome of the T cell response.

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1

G.M. and P.J. are equivalent contributors.

2

Corresponding author. Centre d'Immunologie Pierre Fabre, 5, avenue Napoléon III, F-74164 Saint Julien en Genevois. Fax: +33 4 50 35 35 90. E-mail:[email protected].

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