• Leu-1
• Ly-1
• T1
• Tp67

MAJOR LINKS FOR CD5  

• NCBI LocusLink Record: 921
• Mendelian Inheritance in Man (OMIM): 153340
• SwissProt annotated protein record: P06127

• 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*

CELLULAR FUNCTION OF 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 in thymocytes and B1a cells seems to provide inhibitory signals, while in peripheral mature T lymphocytes it acts as a costimulatory 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
• Modulates T-B lymphocyte interaction-dependent, antibody-mediated immune responses through its interaction with CD5 ligands
• CD5 is the phenotypic marker of a B cell subpopulation (B1a cells) involved in the production of autoreactive antibodies*
• The expression of CD5 regulates responsiveness of human T cells to IL-1

DISEASE RELEVANCE OF CD5 AND FUNCTION OF CD5 IN INTACT ANIMAL  

• CD5 is a phenotypic marker for some B-cell lymphoproliferative disorders (B-CLL, mantle zone lymphoma, Hairy cell leukemia, etc...)
• The B1a (CD5+) population is expanded in some autoimmune disorders (Rheumatoid Arthritis, Sjögren Syndrome, Insulin-dependent Diabetes Mellitus, Graves' disease, etc...)*
• 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 II-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 loss of CD5 expression (and other costimulatory molecules, like CD28 and CD6) in the expanded CD8+ human T cells

• Families in which CD5 is a member
  • CD5-->SRCR group B-->SRCR-->scavenger receptor superfamily

MOLECULAR STRUCTURE OF CD5  

• The extracellular region consists of three scavenger receptor cysteine-rich domains of about 100 amino acids each
• Each domain is encoded by a single exon, as reported for subgroup B SRCR
• The highest amino acid conservation between different animal species is seen at domain 3 (44% homology), and is lowest at domain 1 (25% homology)
• Domain 1 is separated from domain 2 by a connecting peptide rich in Thr and Pro residues which has been highly conserved during phylogeny (74% homology)
• The highly conserved cytoplasmic domain (80% homology) is about 90 residues long and contains multiple potential Ser/Thr and Tyr phosphorylation sites, some of which are included within an ITAM-like motif

MOLECULAR MASS OF CD5  

POST-TRANSCRIPTIONAL MODIFICATION OF CD5  

• No alternative splicing forms reported

POST-TRANSLATIONAL MODIFICATION OF CD5  

• Potential N-glycosylation sites at domains 1 and 2
• Constitutive and inducible Ser/Thr phosphorylation
• Inducible Tyr phosphorylation

SUBSTRATES FOR CD5   - No information

ENZYMES WHICH MODIFY CD5  

LIGANDS FOR CD5 AND MOLECULES ASSOCIATED WITH CD5  

• Expressed at low density early on thymocytes and at high density on all mature T lymphocytes
• Expressed at higher density on Th lymphocytes as compared to Tc lymphocytes*
• 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)

• A key challenge will be the identification of alternative CD5 ligands in humans and the elucidation of its physiological role as a costimulatory or inhibitory receptor*

SELECTION OF OTHER CD5-SPECIFIC REFERENCE MAB  

REVIEWS

1. Kipps TJ. The CD5 B cell. Adv. Immunol. 1988 47:117 PubMed

2. Resnick D, Pearson A and Krieger M. The SRCR superfamily: a family reminiscent of the Ig superfamily. Trends Biochem. Sci. 1993 19:5 PubMed

PRIMARY CITATIONS

3. Alberola-Ila J, Places L, Cantrell DA, Vives J and Lozano F. Intracellular events involved in CD5-induced human T cell activation and proliferation. J. Immunol. 1992 148:1287 PubMed

4. Alberola-Ila J, Places L, Lozano F and Vives J. Association of an activation inducible serine kinase activity with CD5. J. Immunol. 1993 151:4423 PubMed

5. Antin JH, Emerson SG, Martin P, Gadol N and Ault KA. Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies. J. Immunol. 1985 136:505 PubMed

6. Bergui L, Tesio L, Schena M, Riva M, Malavasi F, Schulz T, Marchisio PC and Caligaris-Cappio F. CD5 and CD21 molecules are a functional unit in the cell/substrate adhesion of B-chronic lymphocytic leukemia cells. Eur. J. Immunol. 1988 18:89 PubMed

7. Beyers AD, Spruyt LL and Williams AF. Molecular associations between the T-lymphocyte antigen receptor complex and the surface antigens CD2, CD4, or CD8 and CD5. Proc. Natl. Acad. Sci. U.S.A. 1992 89:2945 PubMed

8. Biancone L, Bowen MA, Lim A, Aruffo A, Andres G and Stamenkovic I. Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes. J. Exp. Med. 1996 184:811 PubMed

9. Bierer BE, Burakoff SJ and Smith BR. A large proportion of T lymphocytes lack CD5 expression after bone marrow transplantation. Blood 1989 73:1359 PubMed

10. Bikah G, Carey J, Ciallella JR, Tarakhovsky A and Bondada S. CD5-mediated negative regulation of antigen receptor-induced growth signals in B-1 B cells. Science 1996 274:1906 PubMed

11. Calvo J, Sole J, Simarro M, Vives J and Lozano F. Evolutionarily conserved transcription regulatory elements within the 5'-flanking region of the human CD5 gene. Tissue Antigens 1996 47:257 PubMed

12. Ceuppens JL, Baroja ML: Monoclonal antibodies to the CD5 antigen can provide the necessary second signal for activation of isolated resting T cells by solid-phase bound OKT3. J Immunol 1986 137: 1816 ** PubMed

13. Davies AA, Ley SC and Crumpton MJ. CD5 is phosphorylated on tyrosine after stimulation of the T-cell antigen receptor complex. Proc. Natl. Acad. Sci. U.S.A. 1992 89:6368 PubMed

14. Dennehy KM, Broszeit R, Garnett D, Durrheim GA, Spruyt LL and Beyers AD. Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5. Eur. J. Immunol. 1997 27:679 PubMed

15. Gary-Gouy H, Lang V, Sarun S, Boumsell L and Bismuth G. In vivo association of CD5 with tyrosine-phosphorylated ZAP-70 and p21 phospho-zeta molecules in human CD3+ thymocytes. J. Immunol. 1997 159:3739 PubMed

16. Jones NH, Clabby ML, Dialynas DP, Huang HJ, Herzenberg LA and Strominger JL. Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1. Nature 1986 323:346 PubMed

17. Lankester AC, van Schijndel GM, Cordell JL, van Noesel CJ and van Lier RA. CD5 is associated with the human B cell antigen receptor complex. Eur. J. Immunol. 1994 24:812 PubMed

18. Ledbetter JA, Parsons M, Martin PJ, Hansen JA, Rabinovitch PS and June CH. Antibody binding to CD5 (Tp67) and Tp44 T cell surface molecules: effects on cyclic nucleotides, cytoplasmic free calcium, and cAMP-mediated suppression. J. Immunol. 1986 137:3299 PubMed

19. Nishimura Y, Bierer BE and Burakoff SJ. Expression of CD5 regulates responsiveness to IL-1. J. Immunol. 1988 141:3438 PubMed

20. Raab M, Yamamoto M and Rudd CE. The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck. Mol. Cell. Biol. 1994 14:2862 PubMed

21. Reinherz EL, Kung PC, Goldstein G and Schlossman SF. A monoclonal antibody with selective reactivity with functionally mature human thymocytes and all peripheral human T cells. J. Immunol. 1979 123:1312 PubMed

22. Simarro M, Pelassy C, Calvo J, Places L, Aussel C and Lozano F. The cytoplasmic domain of CD5 mediates both TCR/CD3-dependent and -independent diacylglycerol production. J. Immunol. 1997 159:4307 PubMed

23. Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Muller W, Killeen N and Rajewsky K. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science 1995 269:535 PubMed

24. Van de Velde H, von Hoegen I, Luo W, Parnes JR and Thielemans K. The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature 1991 351:662 PubMed

25. Vandenberghe P and Ceuppens JL. Immobilized anti-CD5 together with prolonged activation of protein kinase C induce interleukin 2-dependent T cell growth: evidence for signal transduction through CD5. Eur. J. Immunol. 1991 21:251 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov