Differential expression of CD97 on human lymphocyte subsets and limited effect of CD97 antibodies on allogeneic T-cell stimulation

Kop, Else N.; Matmati, Mourad; Pouwels, Walter; Leclercq, Georges; Tak, Paul P.; Hamann, Jörg

doi:10.1016/j.imlet.2009.03.009

Cited by 18 publications

(12 citation statements)

References 54 publications

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“…We observed and validated increased CD97 level in response to IL-2 by real time RT-PCR (Fig. 4a) that was comparable with the results from Kop et al [57]. …”

Section: Resultssupporting

confidence: 91%

Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis

Cao

Kapur

et al. 2013

Journal of Proteomics

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Natural killer (NK) cells efficiently cytolyse tumors and virally infected cells. Despite the important role that interleukin (IL)-2 plays in stimulating the proliferation of NK cells and increasing NK cell activity, little is known about the alterations in the global NK cell proteome following IL-2 activation. To compare the proteomes of naïve and IL-2-activated primary NK cells and identify key cellular pathways involved in IL-2 signaling, we isolated proteins from naïve and IL-2-activated NK cells from healthy donors, the proteins were trypsinized and the resulting peptides were analyzed by 2D LC ESI-MS/MS followed by label-free quantification. In total, more than 2000 proteins were identified from naïve and IL-2-activated NK cells where 383 proteins were found to be differentially expressed following IL-2 activation. Functional annotation of IL-2 regulated proteins revealed potential targets for future investigation of IL-2 signaling in human primary NK cells. A pathway analysis was performed and revealed several pathways that were not previously known to be involved in IL-2 response, including ubiquitin proteasome pathway, integrin signaling pathway, platelet derived growth factor (PDGF) signaling pathway, epidermal growth factor receptor (EGFR) signaling pathway and Wnt signaling pathway.

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“…We observed and validated increased CD97 level in response to IL-2 by real time RT-PCR (Fig. 4a) that was comparable with the results from Kop et al [57]. …”

Section: Resultssupporting

confidence: 91%

Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis

Cao

Kapur

et al. 2013

Journal of Proteomics

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“…We observed and validated increased CD97 level in response to IL-2 by real time RT-PCR (Fig. 4a) that was comparable with the results from Kop et al [57].CD98 is a transmembrane glycoprotein identified as a lymphocyte activation antigen [58,59]. Because the level of CD98 on cell surface was markedly increased in activated lymphocytes, CD98 has been mainly used as a T cell activation marker [58,59] and has been implicated for its role in regulating integrin signaling, amino acid transport and immune response [60,61].…”

supporting

confidence: 91%

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

Patankar¹

2013

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE November 2013 REPORT TYPE Final Report DATES COVERED15 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Wisconsin-Madison, Madison, WI. 53715 PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES 14. ABSTRACT In previous studies we have demonstrated that the ovarian cancer antigen CA125 specifically binds to certain sunsets of immune cell. Based on these observations we have hypothesized that proteomic and transciptomic analysis of immune cells from ovarian cancer patients will result in the identification of specific biomarkers in the immune cells. The current proposal will further investigate this hypothesis by conducting in-depth proteomic analysis of immune cells from cancer patients and healthy blood donors. Studies conducted have resulted in development of streamlined protocols for proteomic analysis of human immune cells. Proteomic analysis of human NK cells has been completed. In addition to proteomic analysis we have also compared the transcriptome of immune cells from ovarian cancer patients and healthy donors and have identified approximately 1600 genes that are differentially expressed in the patient samples. On-going research is focused on validating the proteomic and transcriptome data and demonstrating changes immune cells in response to cancer antigens. iii SUBJECT TERMS IntroductionImmune cells are in continuous crosstalk with tumor cells and other cells in the tumor microenvironment. This crosstalk originates from direct physical contact between the immune cells and the cells in the tumor microenvironment or through their interactions with factors (proteins, lipids and other biomolecules as well as cellular fragments such as exosomes and microparticles) released from the tumors and associated tissues. This interaction causes changes in the molecular make-up of immune cells. In t...

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“…2/2 mice Expression analysis by flow cytometry in wild-type mice revealed a broad distribution of CD97 on almost all leukocytes with, like in humans (33), highest expression levels found on myeloid cells (Fig. 1A).…”

Section: Cd97 Expression On Immune Cells Is Increased In Cd55mentioning

confidence: 85%

“…CD97 and CD55 are abundantly expressed by all types of leukocytes (33,52). Moreover, many epithelial cells express CD97, and CD55 is found on erythrocytes, endothelial cells, and stromal cells (11,26,53).…”

Section: Discussionmentioning

confidence: 99%

Shear Stress–Dependent Downregulation of the Adhesion-G Protein–Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55

Karpus

Veninga

Hoek

et al. 2013

The Journal of Immunology

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Adhesion G protein–coupled receptors (aGPCRs) are two-subunit molecules, consisting of an adhesive extracellular α subunit that couples noncovalently to a seven-transmembrane β subunit. The cooperation between the two subunits and the effect of endogenous ligands on the functioning of aGPCRs is poorly understood. In this study, we investigated the interaction between the pan-leukocyte aGPCR CD97 and its ligand CD55. We found that leukocytes from CD55-deficient mice express significantly increased levels of cell surface CD97 that normalized after transfer into wild-type mice because of contact with CD55 on both leukocytes and stromal cells. Downregulation of both CD97 subunits occurred within minutes after first contact with CD55 in vivo, which correlated with an increase in plasma levels of soluble CD97. In vitro, downregulation of CD97 on CD55-deficient leukocytes cocultured with wild-type blood cells was strictly dependent on shear stress. In vivo, CD55-mediated downregulation of CD97 required an intact circulation and was not observed on cells that lack contact with the blood stream, such as microglia. Notably, de novo ligation of CD97 did not activate signaling molecules constitutively engaged by CD97 in cancer cells, such as ERK and protein kinase B/Akt. We conclude that CD55 downregulates CD97 surface expression on circulating leukocytes by a process that requires physical forces, but based on current evidence does not induce receptor signaling. This regulation can restrict CD97–CD55-mediated cell adhesion to tissue sites.

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Differential expression of CD97 on human lymphocyte subsets and limited effect of CD97 antibodies on allogeneic T-cell stimulation

Cited by 18 publications

References 54 publications

Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis

Differential expression of proteins in naïve and IL-2 stimulated primary human NK cells identified by global proteomic analysis

Mining the Immune Cell Proteome to Identify Ovarian Cancer-Specific Biomarkers

Shear Stress–Dependent Downregulation of the Adhesion-G Protein–Coupled Receptor CD97 on Circulating Leukocytes upon Contact with Its Ligand CD55

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