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 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.
Magistrelli
G
G
Centre d'Immunologie Pierre Fabre, Saint Julien en Genevois, France.
Jeannin
P
P
Elson
G
G
Gauchat
J F
JF
Nguyen
T N
TN
Bonnefoy
J Y
JY
Delneste
Y
Y
D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D018106:CD28 Antigens / Q000235:genetics*; D003600:Cytosol / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism
D018106:CD28 Antigens; D008565:Membrane Proteins; D012333:RNA, Messenger