A secreted form of the human lymphocyte cell surface molecule CD8 arises from alternative splicing.
The human lymphocyte differentiation antigen CD8 is encoded by a single gene that gives rise to a 33- to 34-kDa glycoprotein expressed on the cell surface as a dimer and in higher molecular mass forms. We demonstrate that the mRNA is alternatively spliced so that an exon encoding a transmembrane domain is deleted. This gives rise to a 30-kDa molecule that is secreted and exists primarily as a monomer. mRNA corresponding to both forms is present in peripheral blood lymphocytes, Con A-activated peripheral blood lymphocytes, and three CD8+ T-cell lines, with the membrane form being the major species. However, differences in the ratio of mRNA for membrane CD8 and secreted CD8 exist. In addition, the splicing pattern we observe differs from the pattern found for the mouse CD8 gene. This mRNA is also alternatively spliced, but an exon encoding a cytoplasmic region is deleted, giving rise to a cell surface molecule that differs in its cytoplasmic tail from the protein encoded by the longer mRNA. Neither protein is secreted. This is one of the first examples of a different splicing pattern between two homologous mouse and human genes giving rise to very different proteins. This represents one mechanism of generating diversity during speciation.
Giblin
P
P
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06510.
Ledbetter
J A
JA
Kavathas
P
P
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001483:Base Sequence; D016827:CD8 Antigens; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D002472:Cell Transformation, Viral; D005796:Genes; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D008214:Lymphocytes / Q000276:immunology*; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D012333:RNA, Messenger