CD279 PDC1 (programmed cell death 1), PD1, hPD-1, SLEB2
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
B Cell
Thymocyte
Spleen
Monocyte
Lymph Node
55 / 55

Expression
Analysis of mRNA indicates that the expression of CD279 is associated with cells undergoing classical apoptosis, but not with cells undergoing non-apoptotic PCD.  CD279
is expressed on 3%-5% of normal thymocytes but is expressed during thymic development primarily on ~35% of CD4-/CD8- cells.  Expression is on thymocytes can be divided into 2 distinct populations.  Expression is on double-negative γδ thymocytes and on thymocytes of the ab TCR lineage.  CD279 is expressed on activated T and B cells and on activated monocytes.  NK-T cells express low levels of CD279.  Expression on thymocytes, as well as T cells in the spleen and lymph nodes, can be stimulated in vivo with anti-CD3 antibodies. CD279 expression is not readily detected in the brain, heart, lung or kidney.

Structure
MOLECULAR FAMILY NAME: Belongs to the immunoglobulin gene family.

CD279 is a single-pass type-1 268 aa glycoprotein  It contains a 20 aa signal sequence, an 150 aa extracellular domain which contains an Ig-like V-type domain and 4 potential N-linked glycosylation sites, a 21 aa transmembrane domain and a 97 aa intracellular cytoplasmic domain containing 2 motifs (ITIM and ITSM).  Although both motifs are phosporylated following CD279 ligation, ITSM is required for inhibitory activity.  CD279 encodes a cell surface receptor that is a member of the B7 superfamily involved in immunomodulation and it belongs to the CD28/CD152(CTLA-4) subfamily within the Ig superfamily.  CD279 is monomeric.

MOLECULAR MASS
Cell Type Unreduced Reduced
55 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 4 mRNA isoforms in addition to a full-length form.  One of these isoforms is predicted to be soluble.

POST-TRANSLATIONAL MODIFICATION: No information.

Ligands
LIGANDS AND MOLECULE ASSOCIATED WITH CD279

CD279 binds to CD273 (B7-DC) and CD274 (B7-H1).

Function
CD279 is named programmed death (PD-1) and from mRNA analysis, it appears that CD279 expression is strongly associated with the apoptotic programmed cell death but it has not been shown to induce cell death directly but may do so indirectly.  Cell death may be due in part to CD279 inhibition of cell survival gene bcl-xL expression, down regulation of glucose metabolism, and reduction in Akt activation.  CD279 is an inducible molecule that plays a role in maintaining peripheral self-tolerance and several studies demonstrate that the binding of  CD274/CD279 (PD-L1/PD-1)  interaction is important in preventing autoimmunity.  CD273 ligation of CD279 is associated with inhibition of T cell proliferation and and may contibute to the prevention of autoimmune diseases and peripheral tolerance of T cells.  It has been suggested that CD279 may play a role in clonal selection of lymphocytes.  CD279 is also thought to play a role in pro-B cell differentiation.  In mice, this gene is induced in the thymus when anti-CD3 antibodies are injected and large numbers of thymocytes undergo apoptosis.  Mice deficient for CD279 bred on a BALB/c background developed dialated cardiomyopathy and died from congestive heart failure suggesting this gene is a possible cell death inducer. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD279 IN INTACT ANIMAL

Single nucleotide polymorphisms (SNP) analysis of CD279 are associated in humans with susceptibility to systemic lupus erythematosus (SLE) and the presence of nephropathy in SLE, type 1 diabetes and rheumatoid arthritis and SNPs may be useful in prognostic evaluation of patients for susceptibility to autoimmune diseases.  CD279 deficient mice develop autoimmune conditions including lupus-like glomerulonephritis and proliferative arthritis in C57BL/6 mice and lethal dilated cardiomyopathy mediated by autoantibodies in BALB/c mice.  Mice deficient for CD279 bred on a BALB/c background developed dialated cardiomyopathy and died from congestive heart failure suggesting this gene is a possible cell death inducer. 


Comments
MOLECULAR INTERACTIONS-
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD279: No information

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD279: No information.

ADDITIONAL INSIGHTS

For further information see Ishida, Y. et al (1992) EMBRO J. 11: 3887-3895.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 5133Q15116
MouseS28029Q02242X67914
Antibodies

Revised June 25, 2008


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