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Kummer, U. ; Thierfelder, S. ; Mysliwietz, J.

Antigen Density on Target Cells Determines the Immunosuppressive Potential of Rat IgG2b Monoclonal Antibodies.

Eur. J. Immunol. 20, 107-112 (1990)
DOI
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The current studies were designed to determine the relevance of T cell antigen density, besides antibody isotype, with regard to the success of antibody serotherapy. We compared the immunosuppressive effects of two rat IgG2b monoclonal anti-Thy-1 antibodies, RmT1 and 30-H12, with distinct binding sites in a graft-vs.-host disease (GVHD) model of fully H-2 and I-A region-mismatched bone marrow transplantation, making use of the difference in Thy-1.2 antigen density between homozygous (BALB/c) and heterozygous (BALB/c X AKR/J)F1 GVHD-promoting donor cells. Antibodies RmT1 (directed against a monomorphic determinant on mouse Thy-1) and 30-H12 (reactive with the Thy-1.2 allele-specific determinant) did not differ in their anti-GVHD activity with regard to Thy-1.2 homozygous grafts. However, in the region of a critical number of binding sites a small difference in the amounts of the two antibodies bound (about 8 X 10(3) IgG molecules/cell) obviously accounts for a great difference in anti-GVHD activity. This is shown in a two haplotype host-graft disparity between C57BL/6 recipients treated with either RmT1 or 30-H12 before challenging them with (BALB/c X AKR/J)F1 grafts, where the Thy-1.2 antigen concentration is approximately 50% compared to the density on BALB/c lymphocytes. Here, mAb 30-H12 loses its remarkable in vivo immunosuppressive quality, whereas RmT1 treatment protects mice against lethal GVHD. Binding sites were quantitated using a computerized approach for the analysis of data from ligand binding experiments of the respective mAb, RmT1 and 30-H12, coated to LN cells of BALB/c and F1 hybrid origin. Furthermore, the in vivo immunosuppressive activity of rat IgG2b antibodies directed against Thy-1 was found to correlate with their ability to generate stable antibody-C1q complexes on the cell surface of immunocompetent T cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Zeitschrift European Journal of Immunology
Quellenangaben Band: 20, Heft: 1, Seiten: 107-112 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
Departments & Institutes