Disease relevance of CD6

• As the melanoma cell lines analyzed are all CD6 negative, these results strongly suggest that MEMD/ALCAM is an adhesion molecule mediating homophylic clustering of melanoma cells [1].
• CD6 ligation modulates the Bcl-2/Bax ratio and protects chronic lymphocytic leukemia B cells from apoptosis induced by anti-IgM [2].
• Most B-CLL cells were positive for CD6 and the expression of CD6 was increased after activation with Staphylococcus aureus Cowan I plus interleukin-2 or 12-O-tetradecanoylphorbol 13-acetate, although anti-CD6 antibodies did not increase proliferative responses to these stimuli [2].
• Prediction of graft-versus-host disease by phenotypic analysis of early immune reconstitution after CD6-depleted allogeneic bone marrow transplantation [3].
• We now report on the clinical outcome of 29 patients treated with low-dose IL-2 after CD6-depleted allogenic BMT for hematologic malignancy [4].

Psychiatry related information on CD6

• At T12, after adjusting for training activity, physical activity on training days was significantly lower than on non-training days (23.7 +/- 8.4 vs. 28.2 +/- 9.3 counts x min(-1); p<0.01) [5].
• PARTICIPANTS: Nine men with T5 to T12 paraplegia, 8 of whom had complete lesions and 1 with some sacral sparing (American Spinal Injury Association grade B) without proprioception, matched to 9 able-bodied men [6].

High impact information on CD6

• Conduction to the parietal cortex (T12-P37 interpeak latency) worsened in both the symptomatic men and the boys with preclinical adrenomyeloneuropathy [7].
• Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand [8].
• Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 monoclonal antibody (mAb) or with a mAb (J4-81) that recognized a TE cell antigen [8].
• Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion [8].
• CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation [9].

Chemical compound and disease context of CD6

• Phage T14 encodes the SpeA exotoxin and is closely related to the classic converting phage T12 [10].
• The M phenotype increased since 2000, linked to a decrease of tetracycline resistance, and was predominantly associated with T1 in 2000-2001 and T12 in 2002 among carriage isolates, and with T8/25/Imp19 through 2000-2002 among tonsillitis/pharyngitis isolates [11].
• Cyclic dysmenorrhea was reported by 13 women with injuries ranging from C5 to T12 [12].
• In the diabetic and control groups, after 12 weeks of training the forearm flexor muscles, power output at the intracellular threshold of acidosis (IT) increased (p < .01) similarly: T0 versus T12: 0.90 +/- 0.09 versus 1.20 +/- 0.13 and 1.03 +/- 0.07 versus 1.22 +/- 0.10 W, respectively [13].
• A woman undergoing palliative radiotherapy to the T12 -S2 spine with concurrent bortezomib developed unexpectedly severe, acute radiation enteritis requiring hospital admission [14].

Biological context of CD6

• The membrane-proximal scavenger receptor cysteine-rich domain of CD6 contains the activated leukocyte cell adhesion molecule binding site [15].
• These findings indicate that the CD6-ALCAM interaction results in activation of the three MAPK cascades, likely influencing the dynamic balance that determines whether resting or activated lymphocytes survive or undergo apoptosis [16].
• Cell adhesion assays showed that CD6-ALCAM interactions mediate thymocyte-thymic epithelium cell binding [15].
• The ligation of CD6 induced the transcriptional activation of reporter genes under the control of the c-Fos serum responsive element and AP-1 [16].
• Receptor-ligand binding assays, antibody blocking experiments, and examination of the tissue distribution of these two cell surface proteins suggest that CD6-ALCAM interactions play an important role in mediating the binding of thymocytes to thymic epithelial cells and of T cells to activated leukocytes [17].

Anatomical context of CD6

• Here we show that Tyr residues in the cytoplasmic domain of CD6 become phosphorylated upon T cell activation via the TCR complex [18].
• CD6 is a cell surface receptor primarily expressed on immature thymocytes and mature T and B1a lymphocytes [16].
• Activated leukocyte cell adhesion molecule (ALCAM) was recently identified as a ligand for CD6, a signaling receptor expressed on T cells, a subset of B cells, and some cells in the brain [17].
• Evidence for the expression of a second CD6 ligand by synovial fibroblasts [19].
• Therefore, we propose that syntenin-1 may function as a scaffolding protein coupling CD6 and most likely other lymphocyte receptors to cytoskeleton and/or signaling effectors during IS maturation [20].

Associations of CD6 with chemical compounds

• CD6 is a type I membrane glycoprotein expressed on thymocytes, mature T and B1a lymphocytes, and CNS cells [20].
• The C-terminal cytoplasmic region of CD6, as well as Src tyrosine kinases, was critical for CD6-induced ERK1/2 activation [16].
• The cytoplasmic domain of CD6 contains two serine residues, one or both of which are substrates for phosphorylation during T cell activation [21].
• After maturation of N-linked glycan and addition of sulfated O-linked oligosaccharide, CD6 appears on the cell surface as a molecule of 130 kDa [22].
• CD5 and CD6 co-immunoprecipitate from Brij 96 but not Nonidet P-40 cell lysates, independently of both the co-expression of other lymphocyte surface receptors and the integrity of CD5 cytoplasmic region [23].

Physical interactions of CD6

• In this study, we report that the amino-terminal Ig-like domain of human ALCAM specifically binds to the third membrane-proximal scavenger receptor cysteine-rich (SRCR) domain of human CD6 [17].

Regulatory relationships of CD6

• We also show that activation via CD2 induces CD6 expression on mature human thymocytes and on a subset of immature human thymocytes that are resistant to apoptosis [24].
• Knowledge that CD166 was expressed in normal human salivary epithelium led to these studies of CD166 and CD6 in diseased mouse salivary glands, that resemble pathology seen in the human disease, Sjögren's syndrome [25].
• However, B-CLL cells are CD5 positive and most of them also express CD6, surface receptors that are present in just a small subset of normal B-cells [26].
• CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76 [27].

Other interactions of CD6

• Moreover, the CD6-ALCAM interaction has been shown to be critical for proper immunological synapse maturation and T cell proliferative responses [16].
• Of the T-cell markers, CD5, CD6, and CD7 showed lineage promiscuity by their presence on some B-NHL [28].
• Mitogen-activated protein kinase pathway activation by the CD6 lymphocyte surface receptor [16].
• The present study shows that CD6 ligation with three different specific mAbs (161.8, SPV-L14.2, and MAE1-C10) induces time- and dose-dependent activation of ERK1/2 on normal and leukemic human T cells [16].
• Accordingly, CD6-mediated activation of p38 and JNK was also observed [16].

Analytical, diagnostic and therapeutic context of CD6

• However, the precise biological effects of CD6 ligation and its signaling pathway are still not well understood [16].
• Further confirmation of the CD6-syntenin-1 interaction was obtained from pull-down and co-immunoprecipitation assays in mammalian cells [20].
• Fluorescence in situ hybridization studies and screening of a chromosome-specific YAC (yeast artificial chromosome) library revealed that the gene encoding CD6 is located on chromosome 11 at 11q13 in close proximity to the gene encoding the related molecule CD5 and within 600 kb of CD20 [29].
• CD6 was highly expressed on mouse T cells isolated from the spleen, lymph node and thymus as demonstrated by two-color immunofluorescence analysis [30].
• The apparent discrepancy between the size of the cytoplasmic domain in human (44 amino acids) and mouse (243 amino acids) CD6, led us to use reverse transcriptase-polymerase chain reaction of human peripheral blood lymphocyte mRNA to isolate cDNA clones that include the carboxyl-terminal coding region of human CD6 [31].

References