CD6—ligand interactions: a paradigm for SRCR domain function?

Aruffo, Alejandro; Bowen, Michael A.; Patel, Dhavalkumar D.; Haynes, Barton F.; Starling, Gary C.; Gebe, John A.; Bajorath, Jürgen

doi:10.1016/s0167-5699(97)01130-4

Cited by 138 publications

(125 citation statements)

References 38 publications

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“…31,32 CD166 functions as a ligand for the CD6 receptor, which is expressed on T cells and some B cells. 33,34 The CD6-CD166 interaction facilitates stable cell-cell binding and is involved in the activation of human cd T cells. 31 NKG2D, which is expressed on natural killer cells, CD8 1 lymphocytes and cd T cells, can recognize MICA/B or ULBPs expressed on malignant haematological cells.…”

Section: Discussionmentioning

confidence: 99%

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

et al. 2011

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Cell-based immunotherapy for lymphoid malignancies has gained increasing attention as patients develop resistance to conventional treatments. cd T cells, which have major histocompatibility complex (MHC)-unrestricted lytic activity, have become a promising candidate population for adoptive cell transfer therapy. We previously established a stable condition for expanding cd T cells by using anti-cd T-cell receptor (TCR) antibody. In this study, we found that adoptive transfer of the expanded cd T cells to Daudi lymphoma-bearing nude mice significantly prolonged the survival time of the mice and improved their living status. We further investigated the characteristics of these antibody-expanded cd T cells compared to the more commonly used phosphoantigen-expanded cd T cells and evaluated the feasibility of employing them in the treatment of lymphoid malignancies. Slow but sustained proliferation of human peripheral blood cd T cells was observed upon stimulation with anti-cd TCR antibody. Compared to phosphoantigen-stimulated cd T cells, the antibody-expanded cells manifested similar functional phenotypes and cytotoxic activity towards lymphoma cell lines. It is noteworthy that the anti-cd TCR antibody could expand both the Vd1 and Vd2 subsets of cd T cells. The in vitro-expanded Vd1 T cells displayed comparable tumour cell-killing activity to Vd2 T cells. Importantly, owing to higher C-C chemokine receptor 4 (CCR4) and CCR8 expression, the Vd1 T cells were more prone to infiltrate CCL17-or CCL22-expressing lymphomas than the Vd2 T cells. Characterizing the peripheral blood cd T cells from lymphoma patients further confirmed that the anti-cd TCR antibody-expanded cd T cells could be a more efficacious choice for the treatment of lymphoid malignancies than phosphoantigen-expanded cd T cells.

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Section: Discussionmentioning

confidence: 99%

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

et al. 2011

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“…The SRCR-SF includes both cell-surface and secreted proteins that can be expressed on cells of hemopoietic origin such as macrophages (e.g., SR-AI/II, MARCO, CD163, Mac2-binding protein, and Sp␣) and lymphocytes (e.g., CD5, CD6, and T19/WT1), as well as on nonhematological cells such as those from of the digestive, respiratory, and urinary epithelial tracts (e.g., DMBT1, S4D-SRCRB, and SCARA5) (2). There is no unifying function for all of the members of the SRCR-SF, but some of them have been implicated in the development of the immune system and in the regulation of innate and adaptive immune responses (3). A few members of the SRCR-SF (i.e., SR-AI/II, MARCO, DMBT1, Sp␣, and SCARA5) are known to interact with bacteria and to bind to conserved pathogen-associated molecular patterns present on microbial surfaces, such as LPS, lipoteichoic acid (LTA), and peptidoglycan.…”

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

confidence: 99%

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.

100

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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“…AC005732), echinoderms (4,13), tunicates (accession no. BAA82522.1), sea lampreys (14), as well as various mammals (9,15,16). Two invertebrate members of the SRCR superfamily have been shown to function as cell surface receptors: the purported aggregation receptor of a marine sponge (12) and the sea urchin sperm activation receptor for the egg-jelly peptides (13).…”

mentioning

confidence: 99%

Dynamic expression of multiple scavenger receptor cysteine-rich genes in coelomocytes of the purple sea urchin

Pancer

2000

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

132

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Coelomocytes, the heterogeneous population of sea urchin putative immune cells, were found to express a complex set of transcripts featuring scavenger receptor cysteine-rich (SRCR) repeats. SRCR domains define a metazoan superfamily of proteins, many of which are implicated in development and regulation of the immune system of vertebrates. Coelomocytes transcribe multiple SRCR genes from among a multigene family encoding an estimated number of 1,200 SRCR domains in specific patterns particular to each individual. Transcription levels for given SRCR genes may range from pronounced to undetectable, yet all tested animals harbor the genomic loci encoding these genes. Analysis of several SRCR genes revealed multiple loci corresponding to each type. In the case of one SRCR type, a cluster of at least three genes was detected within a 133-kb bacterial artificial chromosome insert, and conserved as well as unique regions were identified in sequences of three genomic clones derived from a single animal. Array hybridizations with repeated samples of coelomocyte messages revealed substantial alterations in levels of expression of many SRCR genes, with fluctuations of up to 10-fold in 1 week and up to 30-fold over a period of 3 months. This report is the first demonstration of genomic and transcriptional complexity in molecules expressed by invertebrate coelomocytes. The mechanisms controlling SRCR gene expression and the functional significance of this dynamic system await elucidation.

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CD6—ligand interactions: a paradigm for SRCR domain function?

Cited by 138 publications

References 38 publications

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

Anti-γδ TCR antibody-expanded γδ T cells: a better choice for the adoptive immunotherapy of lymphoid malignancies

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

Dynamic expression of multiple scavenger receptor cysteine-rich genes in coelomocytes of the purple sea urchin

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