CD5 Tp67, T1, Leu-1, Ly-1(mouse)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
T Cell
B Cell
T Lymphocyte
B Lymphocyte
58 / 58
67 / 67

Expression
CD5 is expressed early at low density on thymocytes and at high density on all mature T lymphocytes.  It is expressed at higher density on Th lymphocytes as compared to Tc lymphocytes and expressed at low density on a small subset of mature B lymphocytes (B1a cells) which is expanded during fetal life and in several autoimmune disorders as well as in some B cell-derived lymphoproliferative disorders (B-CLL).  In cattle and pigs, CD5 is expressed at high density on peripheral blood ab T cells and at low density on gd T cells yielding a bimodal density profile in 2 parameter dot plot profiles using flow cytometry.


Structure
MOLECULAR FAMILY NAME:  Belongs to the scavenger receptor superfamily.

CD5 is a single-pass type-1 glycoprotein.  It contains an extracellular domain which contains 3 scavenger receptor cysteine-rich domains (SRCR) 100 aa each.  Domain 1 and 2 are separated by a connecting peptide-rich in Thr and Pro residues which has been highly conserved during phylogeny with a 74% homology.  The highest aa conservation between different animal species is seen at domain 3 with a 44% homology, and is lowest at domain 1 with a 25% homology.  There is a transmembrqne domain and a highly conserved cytoplasmic domain with a 80% homology is about 90 aa long containing multiple potential Ser/Thr and Tyr phosphorylation sites, some of which are included within an ITAM-like motif. 

MOLECULAR MASS
Cell Type Unreduced Reduced
Mature lymphocytes 58 kDa 67 kDa

POST-TRANSCRIPTIONAL MODIFICATION

There are no alternative splicing forms reported.

POST-TRANSLATIONAL MODIFICATION

There are potential N-glycosylation sites at domains 1 and 2 in the extracellulqr domain and there is constitutive and inducible Ser/Thr phosphorylation and inducible Tyr phosphorylation in the cytoplasmc domain.


Ligands
CD5 co-precipitates with the TCR and BCR in CD5+ B cells and, more directly, with Lck. A report that CD5 purified from cells binds to CD72 has not been substantiated by functional experiments or biochemical studies.

LIGANDS AND MOLECULES ASSOCIATED WITH CD5
Molecule Comment
CD72 (in man and mouse) Constitutive B cell-specific antigen
gp35-37 (only in mouse) Expressed by activated T and B cells
VH framework regions (only in rabbits)
TCR Associated molecule
CD3 Associated molecule
CD2 Associated molecule
CD4 Associated molecule
CD8 Associated molecule
B cell receptor (BCR) Associated molecule
CD21 Associated molecule
PTP1C Only in thymocytes
ZAP-70 Only in thymocytes
p21 phospho-z Only in thymocytes
PI-3 K Only in thymocytes




Function
A role for CD5 in signal transduction is postulated based on stimulatory effects of mAbs. CD5 is phosphorylated on tyrosine residues on T cell activation.  Thymocytes from CD5 knockout CD5-/- mice gave increased responses to receptor-mediated stimulation.  A role for CD5 in thymocyte selection is suggested by altered expression of TCR when CD5-/- mice were crossed with TCR transgenic mice.  Inhibition of T and B interaction by a mouse CD5 mAb is consistent with a role in cell-cell recognition.  CD5 modulates signaling through the antigen-specific receptor complex, TCR and BCR, as deduced from data on CD5 KO mice and from the mitogenic effects of some anti-CD5 mAbs.  CD5 on thymocytes and B1a cells seems to provide inhibitory signals, while on peripheral mature T lymphocytes it acts as a co-stimulatory signal receptor.  CD5 may thus serve as a dual receptor, giving either stimulatory or inhibitory signals depending both on the cell type and the development stage.  CD5-mediated cellular interactions may influence thymocyte maturation and selection.  CD5 modulates T and B lymphocyte interaction-dependent, and antibody-mediated immune responses through its interaction with CD5 ligands.  CD5 is the phenotypic marker of a B cell subpopulation, B 1a cells, involved in the production of autoreactive antibodies.  The expression of CD5 regulates responsiveness of human T cells to IL-1.

BIOCHEMICAL ACTIVITY

As reported for other accessory molecules, CD5 is a signal transducing molecule whose cytoplasmic tail is devoid of any intrinsic catalytic activity. CD5 crosslinking induces extracellular Ca2+ mobilization, tyrosine phosphorylation of intracellular proteins and DAG production. Preliminary evidence shows either functional or physical protein associations with PTP1C, ZAP-70, p56lck, p59fyn, PC-PLC, PI 3-kinase, Ca2++/calmodulin-dependent kinase type IV and an uncharacterized inducible Ser/Thr kinase.

DISEASE RELEVANCE AND FUNCTION OF CD5 IN INTACT ANIMAL

CD5 is a phenotypic marker for some B-cell lymphoproliferative disorders such as B-CLL, mantle zone lymphoma, and hairy cell leukemia.  The CD5+, B1a population is expanded in some autoimmune disorders like rheumatoid arthritis, Sjogren syndrome, insulin-dependent diabetes mellitus, and Graves' disease.  In vivo down-modulation of CD5 by mAbs induces T cell unresponsiveness, and is reported to prevent experimental autoimmune encephalomyelitis in the rat.  Anti-CD5 antibody treatment has a partial therapeutic effect on collagen type 2-induced arthritis in DBA/1 mice and on GVHD after allogeneic marrow transplantation in humans.  The frequency of CD3+ T cells that lack expression of CD5 is dramatically increased following bone marrow transplantation and correlates with the presence of GVHD.  Soluble human recombinant CD5 receptor globulin prevents the development of antibody-mediated membranous glomerulonephritis in mice.  Herpes virus infections induce the loss of CD5 expression and other co-stimulatory molecules, like CD28 and CD6 in the expanded CD8+ human T cells.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD5
Molecule Comments
Ets  Related transcription factors
PKC-inducuble transcription factors
Ras-dependent transcription factors

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD5
Molecules Comment
p56 lck Induces Tyr-phosphorylation after TCR/CD3 crosslinking
Serine kinase Still uncharacterized

ADDITIONAL INSIGHTS

A key challenge will be the identification of alternative CD5 ligands in humans and the elucidation of its physiological role as a co-stimulatory or inhibitory receptor.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 921P06127
MouseA29079P13379M15177
RatP51882D10728
Antibodies
2-176   View Reactivity
25.91   View Reactivity
9G12   View Reactivity
B29A   View Reactivity
BAGB145A   View Reactivity
BAQ43A   View Reactivity
BAQ93A   View Reactivity
BL1A   View Reactivity
CACT105A   View Reactivity
CC17   View Reactivity
CD5-5D7   View Reactivity
CVS5   View Reactivity
DH13A   View Reactivity
DH14A   View Reactivity
DH3B   View Reactivity
FE1.1B11   View Reactivity
GR60A   View Reactivity
HB19A   View Reactivity
HT23A   View Reactivity
LT3A   View Reactivity
LT4A   View Reactivity
LT7A   View Reactivity
MUC1A   View Reactivity
PG114A   View Reactivity
ST1   View Reactivity
UCHT2   View Reactivity
YKIX322.3   View Reactivity

Revised June 25, 2008


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