| Autor: |
Declerck, Paul J., Carmeliet, Peter, Verstreken, Maria, De Cock, Frans, Collen, Désiré |
| Zdroj: |
Journal of Biological Chemistry; April 1995, Vol. 270 Issue: 15 p8397-8400, 4p |
| Abstrakt: |
Induction of an immune response is strongly dependent on the phylogenetic distance between antigen and recipient. In general, antibodies will not be raised against self-antigens nor against highly conserved domains. In the present study we describe the production and characterization of murine monoclonal “auto-antibodies” against murine tissue-type plasminogen activator (t-PA) raised in “knock-out” mice, homozygously deficient of the functional gene. 203 stable hybridomas were obtained producing murine monoclonal antibodies against murine t-PA. Analysis of the species reactivity revealed that 182 cross-reacted with one or more (t-)PAs originating from other species including rat t-PA, human t-PA, and vampire bat-PA. 121 reacted with epitopes conserved among murine, rat, and human t-PA. In addition, 31 of the monoclonal antibodies were directed against domains present in all four species. Epitope mapping indicated a high frequency of specificity toward diverse epitopes that are highly conserved across species. Comparative analysis of their influence on the enzymatic activity of t-PA and their species cross-reactivity clearly demonstrated that the domains required for the biological activity of plasminogen activators are more conserved (p< 0.02) than non-functional domains. |
| Databáze: |
Supplemental Index |
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