Identification of three alternatively spliced variants of human CD28 mRNA

CD28, expressed by T cells, plays a central role in providing costimulatory signals to T cells. The cd28 gene is organized into 4 exons. An alternativ ely spliced CD28 mRNA lacking most of the exon 2 has been previously eviden ced. We report here that non stimulated human T cells express three additio nal alternatively spliced variants of CD28 mRNA (CD28a-c) in. The CD28a var iant, expressed at similar levels to that of the full length CD28 mRNA enco ding for the membrane form, lacks exon 3. This deletion introduces (i) a fr ame shift resulting in the addition of two extra amino acids and a prematur e stop codon and, (ii) induces the loss of the transmembrane region, sugges ting that it could encodes for a soluble monomeric molecule which conserves the binding sites of CD28. The CD28b and CD28c variants, expressed at a lo w level compared with CD28a, are generated by deletion of most of the 3' en d of exon 2 plus exon 3 and exon 2 plus exon 3, respectively. Activated T c ells express only the membrane CD28 mRNA These results suggest that resting human T cells may constitutively express both membrane and soluble CD28 wh ich can differentially regulate the outcome of the T cell response, (C) 199 9 Academic Press.