Alternative splice variants of the human PD-1 gene.
PD-1 is an immunoregulatory receptor expressed on the surface of activated T cells, B cells, and monocytes. We describe four alternatively spliced PD-1 mRNA transcripts (PD-1Deltaex2, PD-1Deltaex3, PD-1Deltaex2,3, and PD-1Deltaex2,3,4) in addition to the full length isoform. PD-1Deltaex2 and PD-1Deltaex3 are generated by alternative splicing where exon 2 (extracellular IgV-like domain) and exon 3 (transmembrane domain) respectively are spliced out. PD-1Deltaex3 is therefore likely to encode a soluble form of PD-1. PD-1Deltaex2,3 lacks exon 2 and 3. These three variants have unaffected open reading frames. PD-1Deltaex2,3,4 lacks exon 2, 3, and 4 (intracellular domain) and contains a premature stop codon in exon 5. Activation of human PBMCs with anti-CD3+anti-CD28 monoclonal antibodies induces an increased level of each PD-1 transcript. A parallel increase in the expression of PD-1Deltaex3 and flPD-1 upon activation suggests an important interplay between the putative soluble PD-1 and flPD-1 possibly involved in maintenance of peripheral self-tolerance and prevention of autoimmunity.
Nielsen
Christian
C
Department of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Ohm-Laursen
Line
L
Barington
Torben
T
Husby
Steffen
S
Lillevang
Søren T
ST
D017398:Alternative Splicing / Q000235:genetics*; D015703:Antigens, CD; D000954:Antigens, Surface / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism; D016133:Polymerase Chain Reaction; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012995:Solubility
D015703:Antigens, CD; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D012333:RNA, Messenger