THE HUMAN PD-1 GENE - COMPLETE CDNA, GENOMIC ORGANIZATION, AND DEVELOPMENTALLY-REGULATED EXPRESSION IN B-CELL PROGENITORS

We report the complete cDNA sequence and the genomic structure of the human PD-1 homologue. An analysis of the expression pattern of the hum an PD-1 gene (hPD-1) and the murine PD-1 gene (mPD-1) in developing bo ne marrow B-lineage cells was also undertaken. The full length hPD-1 c DNA is 2106 nucleotides long and encodes a predicted protein of 288 am ino acid residues. The hPD-1 and mPD-1 genes share 70% homology at the nucleotide level and 60% homology at the amino acid level. Four poten tial sites for N-linked glycosylation are conserved, as are a stretch of amino acids between two cysteine residues resembling a V-set immuno globulin domain, and another region containing a motif similar to an i mmunoreceptor tyrosine-based inhibitory motif. Isolation of the genomi c locus of the hPD-1 gene reveals that the gene is composed of five ex ons located on human chromosome 2 at band q37. The 5' flanking region lacks TATA and CAAT cis-acting elements, but includes a number of pote ntial transcription factor binding sites and a dominant transcription start site, The mPD-1 gene was preferentially expressed in pro-B cells from murine adult bone marrow. Although hPD-1 was not preferentially expressed in pro-B cells from human fetal bone marrow, treatment of is olated pro-B cells with interleukin-7 resulted in a dramatic increase in expression. These data suggest that PD-1 may play a role in B-cell differentiation during the pro-B cell stage. (C) 1997 Elsevier Science B.V.