• T12

MAJOR LINKS FOR CD6  

• NCBI LocusLink Record: 923
• Mendelian Inheritance in Man (OMIM): 186720
• SwissProt annotated protein record: P30203

CELLULAR FUNCTION OF CD6  

• CD6 is an adhesion molecule mediating the binding of developing thymocytes with thymic epithelial cells
• Mabs to CD6 have been shown to either enhance or inhibit the autologous mixed leukocyte reactions (MLR)
• Co-ligation of CD3 and CD6 leads to Ca++ flux
• There is evidence that CD6 ligation by mAbs directly stimulates T-Cells in the presence of macrophages
• CD6 is co-stimulatory with CD3 or PMA

DISEASE RELEVANCE OF CD6 AND FUNCTION OF CD6 IN INTACT ANIMAL  

• May be involved in autoimmunity and graft vs. host disease
• CD6- T cells are less autoreactive than CD6+ T cells and antibodies to CD6 (T12) have long been used to deplete T cells from bone marrow transplants to prevent graft vs. host disease

• Families in which CD6 is a member
  • CD6-->SRCR group B-->SRCR-->scavenger receptor superfamily

MOLECULAR STRUCTURE OF CD6  

• Single chain type I transmembrane molecule of 668 (predicted, human) amino acids containing 3 extracellular SRCR domains

MOLECULAR MASS OF CD6  

POST-TRANSCRIPTIONAL MODIFICATION OF CD6  

• In humans, alternative splice variants have been isolated by RT-PCR from normal lymphocytes, which are predicted to result in molecules with different cytoplasmic tail regions - long (244 aa) mid length (212aa), and short (171aa)
• Two additional splice variants have also been isolated from a patient with B cell chronic lymphocytic leukemia (B-CLL)

POST-TRANSLATIONAL MODIFICATION OF CD6  

• CD6 is extensively glycosylated
• Phosphorylation of serine and threonine residues occurs constitutively in phytoheamagglutinin (PHA) blasts. Tyrosines on CD6 are phosphorylated and serines hyperphosphorylated upon stimulation through the TCR complex*

SUBSTRATES FOR CD6   - No information

ENZYMES WHICH MODIFY CD6   - No information

LIGANDS FOR CD6 AND MOLECULES ASSOCIATED WITH CD6  

• Expressed at low levels on immature thymocytes, and at high levels on mature thymocytes
• CD6 is also expressed on the majority of peripheral blood T cells, a subset of B cells, and may be expressed on a subset of neurons

SELECTION OF OTHER CD6-SPECIFIC REFERENCE MAB  

REVIEWS

1. Aruffo A, Bowen MA, Patel DD, Haynes BF, Starling GC, Gebe JA and Bajorath J. CD6-ligand interactions: a paradigm for SRCR domain function? Immunol. Today 1997 18:498 PubMed

PRIMARY CITATIONS

2. Aruffo A, Melnick MB, Linsley PS and Seed B. The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins. J. Exp. Med. 1991 174:949 PubMed

3. Bowen MA, Patel DD, Li X, Modrell B, Malacko AR, Wang WC, Marquardt H, Neubauer M, Pesando JM, Francke U and et al. Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand. J. Exp. Med. 1995 181:2213 PubMed

4. Bowen MA, Whitney GS, Neubauer M, Starling GC, Palmer D, Zhang J, Nowak NJ, Shows TB and Aruffo A. Structure and chromosomal location of the human CD6 gene: detection of five human CD6 isoforms. J. Immunol. 1997 158:1149 PubMed

5. Gangemi RM, Swack JA, Gaviria DM and Romain PL. Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes. J. Immunol. 1989 143:2439 PubMed

6. Patel DD, Wee SF, Whichard LP, Bowen MA, Pesando JM, Aruffo A and Haynes BF. Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells. J. Exp. Med. 1995 181:1563 PubMed

7. Patel DD, Wee SF, Whichard LP, Bowen MA, Pesando JM, Aruffo A and Haynes BF. Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells. J. Exp. Med. 1995 181:1563 PubMed

8. Robinson WH, Neuman de Vegvar HE, Prohaska SS, Rhee JW and Parnes JR. Human CD6 possesses a large, alternatively spliced cytoplasmic domain. Eur. J. Immunol. 1995 25:2765 PubMed

9. Starling GC, Whitney GS, Siadak AW, Llewellyn MB, Bowen MA, Farr AG and Aruffo AA. Characterization of mouse CD6 with novel monoclonal antibodies which enhance the allogeneic mixed leukocyte reaction. Eur. J. Immunol. 1996 26:738 PubMed

10. Wee S, Wang WC, Farr AG, Nelson AJ, Patel DD, Haynes BF, Linsley PS and Aruffo A. Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues. Cell. Immunol. 1994 158:353 PubMed

11. Whitney GS, Starling GC, Bowen MA, Modrell B, Siadak AW and Aruffo A. The membrane-proximal scavenger receptor cysteine-rich domain of CD6 contains the activated leukocyte cell adhesion molecule binding site. J. Biol. Chem. 1995 270:18187 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