Alternative splice variants of the human PD-1 gene

Cell Immunol. 2005 Jun;235(2):109-16. doi: 10.1016/j.cellimm.2005.07.007. Epub 2005 Sep 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics*
  • Antigens, CD
  • Antigens, Surface / genetics*
  • Apoptosis Regulatory Proteins / genetics*
  • Exons / genetics
  • Gene Expression Regulation
  • Humans
  • Leukocytes / metabolism
  • Polymerase Chain Reaction
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Solubility


  • Antigens, CD
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger