The Accessory Molecules CD5 and CD6 Associate on the Membrane of Lymphoid T Cells

Gimferrer, Idoia; Farnós, Montse; Calvo, Marı́a; Mittelbrunn, Marı́a; Enrich, Carlos; Sánchez-Madrid, Francisco; Vives, Jordi; Lozano, Francisco

doi:10.1074/jbc.m209591200

Cited by 69 publications

(77 citation statements)

References 60 publications

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“…The cell lines COS-7, Raji, K562, and HUT-78 were from the American Type Culture Collection (Manassas, VA). The CD5-and CD6-negative 2G5 cells (20) were stably transfected with the pH␤-CD6.P527stop and pH␤-CD6.wt constructs (12,22). Cell growth conditions are detailed in supporting information (SI) Methods.…”

Section: Methodsmentioning

confidence: 99%

“…They exhibit important differences in their cytoplasmic regions, but their extracellular regions are exclusively composed of three consecutive SRCR domains, which show extensive amino acid sequence identity (1,10). Functionally, they are physically associated to the antigenspecific receptor complex present on T (TCR/CD3) and B (BCR) cells, where they contribute to either positive or negative modulation of the activation and differentiation signals delivered by that receptor complex (2,11,12). In the present study we have explored the bacterial binding capabilities of the ectodomains of the human lymphocyte receptors CD5 and CD6, both known to exist as membrane receptors, but also as soluble receptors circulating in serum (13,14).…”

Section: T He Scavenger Receptor Cysteine-rich Superfamily (Srcr-sf)mentioning

confidence: 99%

“…The recombinant proteins were expressed in HEK 293-EBNA and affinity-purified as reported (12,37). Their purity was assessed by SDS/PAGE and staining with Coomassie blue.…”

Section: Expression Affinity Purification and Biotin Labeling Of Rementioning

confidence: 99%

“…Immunoprecipitation of membrane CD6 (mCD6) from HUT-78 T cells was performed and analyzed by Western blotting as described (12).…”

Section: Binding Assays Of Soluble Proteins To Fitc-re-lpsmentioning

confidence: 99%

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CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Sarrias

Farnós

Mota

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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102

118

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CD6 is a lymphocyte receptor that belongs to the scavenger receptor cysteine-rich superfamily. Because some members of the scavenger receptor cysteine-rich superfamily act as pattern recognition receptors for microbial components, we studied whether CD6 shares this function. We produced a recombinant form of the ectodomain of CD6 (rsCD6), which was indistinguishable (in apparent molecular mass, antibody reactivity, and cell binding properties) from a circulating form of CD6 affinity-purified from human serum. rsCD6 bound to and aggregated several Gram-positive and -negative bacterial strains through the recognition of lipoteichoic acid and LPS, respectively. The K d of the LPS-rsCD6 interaction was 2.69 ؎ 0.32 ؋ 10 ؊8 M, which is similar to that reported for the LPS-CD14 interaction. Further experiments showed that membrane CD6 also retains the LPS-binding ability, and it results in activation of the MAPK signaling cascade. In vivo experiments demonstrated that i.p. administration of rsCD6 before lethal LPS challenge significantly improved mice survival, and this was concomitant with reduced serum levels of the proinflammatory cytokines TNF-␣, IL6, and IL-1␤. In conclusion, our results illustrate the unprecedented bacterial binding properties of rsCD6 and support its therapeutic potential for the intervention of septic shock syndrome or other inflammatory diseases of infectious origin.bacterial cell component ͉ innate immunity ͉ lymphocyte surface receptor

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Section: Methodsmentioning

confidence: 99%

Section: T He Scavenger Receptor Cysteine-rich Superfamily (Srcr-sf)mentioning

confidence: 99%

“…The recombinant proteins were expressed in HEK 293-EBNA and affinity-purified as reported (12,37). Their purity was assessed by SDS/PAGE and staining with Coomassie blue.…”

Section: Expression Affinity Purification and Biotin Labeling Of Rementioning

confidence: 99%

“…Immunoprecipitation of membrane CD6 (mCD6) from HUT-78 T cells was performed and analyzed by Western blotting as described (12).…”

Section: Binding Assays Of Soluble Proteins To Fitc-re-lpsmentioning

confidence: 99%

See 2 more Smart Citations

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

Sarrias

Farnós

Mota

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

102

118

View full text Add to dashboard Cite

show abstract

“…CD6 is recruited to the center of Ag-induced mature IS, where it physically associates and colocalizes with the TCR/ CD3 complex and CD5 (16,17). To further validate the in vivo relevance of the CD6/syntenin-1 interaction, we investigated a possible colocalization of syntenin-1 at the mature IS.…”

Section: Colocalization Studies Of Cd6 and Syntenin-1 In Human Lymphomentioning

confidence: 99%

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

Gimferrer

Ibáñez

Farnós

et al. 2005

The Journal of Immunology

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CD6 is a type I membrane glycoprotein expressed on thymocytes, mature T and B1a lymphocytes, and CNS cells. CD6 binds to activated leukocyte cell adhesion molecule (CD166), and is considered as a costimulatory molecule involved in lymphocyte activation and thymocyte development. Accordingly, CD6 partially associates with the TCR/CD3 complex and colocalizes with it at the center of the mature immunological synapse (IS) on T lymphocytes. However, the signaling pathway used by CD6 is still mostly unknown. The yeast two-hybrid system has allowed us the identification of syntenin-1 as an interacting protein with the cytoplasmic tail of CD6. Syntenin-1 is a PDZ (postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1) domain-containing protein, which functions as an adaptor protein able to bind cytoskeletal proteins and signal transduction effectors. Mutational analyses showed that certain amino acids of the most C-terminal sequence of CD6 (-YDDISAA) and the two postsynaptic density protein-95, postsynaptic discs large, and zona occludens-1 domains of syntenin-1 are relevant to the interaction. Further confirmation of the CD6-syntenin-1 interaction was obtained from pull-down and coimmunoprecipitation assays in mammalian cells. Image analyses also showed that syntenin-1 accumulates at CD6 caps and at the IS. 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.

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The Cd6 gene as a permissive locus for targeted transgenesis in the mouse

Ichise

Sasanuma

et al. 2014

Genesis

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The introduction of a transgene into the genome through homologous recombination or sequence-specific enzymatic modification is a key technique for producing transgenic mice. The Rosa26 gene has been widely used to produce transgenic mice because the gene is transcriptionally active in various cell types and, at many developmental stages, is permissive for constitutive expression of integrated transgenes, and is dispensable for normal development. However, permissive loci other than Rosa26 are needed to generate mice that harbor multiple transgenes for complex studies. Here, we identified the Cd6 locus on mouse chromosome 19 as a transgene integration site in a transgenic mouse strain showing widespread reporter expression. Using this locus, we generated a knock-in mouse line that harbors a CAG promoter-driven reporter transgene, and found that the homozygous transgenic mice are viable and fertile, although transgene insertion disrupted Cd6 gene expression. The transgene on the Cd6 locus expressed reporter genes extensively throughout embryos, neonates, and adults. Combined with the Cre/loxP binary system, blood and lymphatic endothelial cell-specific reporter expression from the transgenic locus was achieved. These results suggest that Cd6 is valuable as an alternative site for targeted transgenesis.

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The Accessory Molecules CD5 and CD6 Associate on the Membrane of Lymphoid T Cells

Cited by 69 publications

References 60 publications

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

CD6 binds to pathogen-associated molecular patterns and protects from LPS-induced septic shock

The Lymphocyte Receptor CD6 Interacts with Syntenin-1, a Scaffolding Protein Containing PDZ Domains

The Cd6 gene as a permissive locus for targeted transgenesis in the mouse

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