Alternatively spliced mRNA encodes a secreted form of human CD8 alpha. Characterization of the human CD8 alpha gene.
We have determined the organization and nucleotide sequence of the gene encoding the human T cell surface glycoprotein CD8 alpha. This gene spans approximately 8 kb and is organized into six exons which encode separate functional domains of the protein. Exon 1 encodes the 5' untranslated region and leader peptide, exon II the Ig V-like region, exon III the hinge-like region, exon IV the transmembrane domain, and exons V and VI the cytoplasmic tail. Alternative splicing that excludes nucleotide sequences from exon IV results in a transcript which encodes a secreted form of the protein. This transcript accounts for approximately 15% of the total CD8 alpha mRNA in human T cell leukemia lines and in normal human tissues. Secreted CD8 alpha protein can be detected in culture supernatants of T cell leukemia lines and PHA-stimulated PBMC by immunoprecipitation with the anti-CD8 alpha mAb OKT8 or with a polyclonal rabbit antiserum specific for the 28 amino acid cytoplasmic domain of CD8 alpha. The secreted CD8 alpha protein forms homodimers; when analyzed by SDS-PAGE, the protein migrates with an apparent molecular mass of 27 or 54 kDa under reducing or non-reducing conditions, respectively. Human secreted CD8 alpha may serve an immunoregulatory role for the interactions of T cells with their targets in vivo.
Norment
A M
AM
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Lonberg
N
N
Lacy
E
E
Littman
D R
DR
D000595:Amino Acid Sequence; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D016827:CD8 Antigens; D005796:Genes; D006801:Humans; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics*; D011994:Recombinant Proteins / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D012333:RNA, Messenger; D011994:Recombinant Proteins