Genomic characterization of CD84 reveals the existence of five isoforms differing in their cytoplasmic domains

CD84, a new member of the immunoglobulin superfamily, shows high homology: with several molecules belonging to the CD2 family of differentiation antig ens. By screening a peripheral blood leukocyte cDNA library four CD84 isofo rms were obtained differing in their 3' sequence. A reverse transcription-p olymerase chain reaction (RT-PCR) analysis confirmed that these isoforms we re normally found on leukocytes: and a new isoform was identified. To estab lish the nature of the five isoforms obtained (CD84a, CD84b, CD84c, CD84d a nd CD84e) the genomic structure of the CD84 gene was determined. Our result s show that it is composed of at least eight exons, with an exon coding for the 5' UTR and the leader peptide, two exons coding for each of the two im munoglobulinlike domains, an exon encoding the transmembrane portion and fo ur exons coding for the cytoplasmic do mains. The isoforms are generated by several mechanisms: alternative use of exons, reading frame shift, use of a cryptic splice site or absence of splicing. The differential expression o f several potentially phosphorylatable residues on the different isoforms c ould be a way to regulate its possible activity in signal transduction.