International Immunology, Vol. 11, No. 5, 777-786,
May 1999
© 1999 Japanese Society for Immunology
T cell activation-associated epitopes of CD147 in regulation of the T cell response, and their definition by antibody affinity and antigen density
ern
1,2
ej
í1
Institute of Immunology–Vienna International Research Cooperation Center at NFI, University of Vienna, Brunner Strasse 59, 1235 Vienna, Austria
1 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague 4, Czech Republic
2 Faculty of Sciences, Charles University, 142 20 Prague 4, Czech Republic
3 Institute of Molecular Pathology, 1030 Vienna, Austria
Correspondence to: H. Stockinger
CD147 is a broadly expressed cell surface glycoprotein of the Ig superfamily whose expression is up-regulated upon T cell activation. In order to elucidate a possible role of CD147 in T cell biology, we established 15 specific mAb. Seven distinct epitopes were defined by the mAb panel. Most of the mAb bound only to phytohemagglutinin (PHA)-activated but not resting T cells. We demonstrate that this was not because of true expression of activation-dependent neoepitopes but rather due to bivalent binding of the relatively low-affinity mAb (affinity constant KA values between 2.25 x 108 and 7 x 109 M–1) to the more densely expressed and/or more clustered CD147 molecules on the activated T cells. In contrast, the mAb with higher affinity (KA > 7 x 109 M–1) could stably bind in a monovalent fashion even to the relatively low dense CD147 molecules on resting T cells. This model might more generally explain the nature of `activation epitopes' described previously in other leukocyte surface molecules. Finally, we provide evidence that induction of ordered dimerization of CD147 by a mAb directed to a unique epitope results in strong inhibition of CD3-mediated T cell activation.
Keywords: antibodies, cell surface molecules, human, T lymphocytes, signal transduction
The first two authors contributed equally to this work
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. S. Vetrivel, X. Zhang, X. Meckler, H. Cheng, S. Lee, P. Gong, K. O. Lopes, Y. Chen, N. Iwata, K.-J. Yin, et al. Evidence That CD147 Modulation of {beta}-Amyloid (A{beta}) Levels Is Mediated by Extracellular Degradation of Secreted A{beta} J. Biol. Chem., July 11, 2008; 283(28): 19489 - 19498. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ruiz, A. Castro-Castro, and X. R. Bustelo CD147 Inhibits the Nuclear Factor of Activated T-cells by Impairing Vav1 and Rac1 Downstream Signaling J. Biol. Chem., February 29, 2008; 283(9): 5554 - 5566. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Damsker, M. I. Bukrinsky, and S. L. Constant Preferential chemotaxis of activated human CD4+ T cells by extracellular cyclophilin A J. Leukoc. Biol., September 1, 2007; 82(3): 613 - 618. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xiao, N. Najafian, J. Reddy, M. Albin, C. Zhu, E. Jensen, J. Imitola, T. Korn, A. C. Anderson, Z. Zhang, et al. Differential engagement of Tim-1 during activation can positively or negatively costimulate T cell expansion and effector function J. Exp. Med., July 9, 2007; 204(7): 1691 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. MacMillan, D. Couriel, D. J. Weisdorf, G. Schwab, N. Havrilla, T. R. Fleming, S. Huang, L. Roskos, S. Slavin, R. K. Shadduck, et al. A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease Blood, March 15, 2007; 109(6): 2657 - 2662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Gwinn, J. M. Damsker, R. Falahati, I. Okwumabua, A. Kelly-Welch, A. D. Keegan, C. Vanpouille, J. J. Lee, L. A. Dent, D. Leitenberg, et al. Novel Approach to Inhibit Asthma-Mediated Lung Inflammation Using Anti-CD147 Intervention J. Immunol., October 1, 2006; 177(7): 4870 - 4879. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Intasai, S. Mai, W. Kasinrerk, and C. Tayapiwatana Binding of multivalent CD147 phage induces apoptosis of U937 cells Int. Immunol., July 1, 2006; 18(7): 1159 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. H. Yang, O. V. Kovalenko, T. V. Kolesnikova, M. M. Andzelm, E. Rubinstein, J. L. Strominger, and M. E. Hemler Contrasting Effects of EWI Proteins, Integrins, and Protein Palmitoylation on Cell Surface CD9 Organization J. Biol. Chem., May 5, 2006; 281(18): 12976 - 12985. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xu and M. E. Hemler Metabolic Activation-related CD147-CD98 Complex Mol. Cell. Proteomics, August 1, 2005; 4(8): 1061 - 1071. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Yang, O. V. Kovalenko, W. Tang, C. Claas, C. S. Stipp, and M. E. Hemler Palmitoylation supports assembly and function of integrin-tetraspanin complexes J. Cell Biol., December 20, 2004; 167(6): 1231 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Tang, S. B. Chang, and M. E. Hemler Links between CD147 Function, Glycosylation, and Caveolin-1 Mol. Biol. Cell, September 1, 2004; 15(9): 4043 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Reimers, K. Zafrakas, V. Assmann, C. Egen, L. Riethdorf, S. Riethdorf, J. Berger, S. Ebel, F. Janicke, G. Sauter, et al. Expression of Extracellular Matrix Metalloproteases Inducer on Micrometastatic and Primary Mammary Carcinoma Cells Clin. Cancer Res., May 15, 2004; 10(10): 3422 - 3428. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Tang and M. E. Hemler Caveolin-1 Regulates Matrix Metalloproteinases-1 Induction and CD147/EMMPRIN Cell Surface Clustering J. Biol. Chem., March 19, 2004; 279(12): 11112 - 11118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Staffler, A. Szekeres, G. J. Schutz, M. D. Saemann, E. Prager, M. Zeyda, K. Drbal, G. J. Zlabinger, T. M. Stulnig, and H. Stockinger Selective Inhibition of T Cell Activation Via CD147 Through Novel Modulation of Lipid Rafts J. Immunol., August 15, 2003; 171(4): 1707 - 1714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Allain, C. Vanpouille, M. Carpentier, M.-C. Slomianny, S. Durieux, and G. Spik Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix PNAS, February 20, 2002; (2002) 52284899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. A. Shackel, P. H. McGuinness, C. A. Abbott, M. D. Gorrell, and G. W. McCaughan Insights into the Pathobiology of Hepatitis C Virus-Associated Cirrhosis : Analysis of Intrahepatic Differential Gene Expression Am. J. Pathol., February 1, 2002; 160(2): 641 - 654. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Burke-Gaffney, K. Blease, A. Hartnell, and P. G. Hellewell TNF-{alpha} Potentiates C5a-Stimulated Eosinophil Adhesion to Human Bronchial Epithelial Cells: A Role for {alpha}5{beta}1 Integrin J. Immunol., February 1, 2002; 168(3): 1380 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Deeg, B. R. Blazar, B. J. Bolwell, G. D. Long, F. Schuening, J. Cunningham, R. M. Rifkin, S. Abhyankar, A. D. Briggs, R. Burt, et al. Treatment of steroid-refractory acute graft-versus-host disease with anti-CD147 monoclonal antibody ABX-CBL Blood, October 1, 2001; 98(7): 2052 - 2058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Sun and M. E. Hemler Regulation of MMP-1 and MMP-2 Production through CD147/Extracellular Matrix Metalloproteinase Inducer Interactions Cancer Res., March 1, 2001; 61(5): 2276 - 2281. [Abstract] [Full Text]
|
|
|
|
|
|
F. Allain, C. Vanpouille, M. Carpentier, M.-C. Slomianny, S. Durieux, and G. Spik Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix PNAS, March 5, 2002; 99(5): 2714 - 2719. [Abstract] [Full Text] [PDF]
|
|