An epitope on the transferrin receptor preferentially exposed during tumor progression in human lymphoma is close to the ligand binding site.
We have previously reported an anti-transferrin receptor antibody, Trump, which was originally selected for its ability to discriminate low- and high-grade lymphomas. This feature was distinct from the other anti-transferrin receptor antibodies such as OKT9. In the present study, further immunochemical analysis was performed to define the nature of the antigenic site recognized by the Trump antibody. Trump was found to block the binding of transferrin both to solubilized and to surface transferrin receptors; conversely, transferrin could block the binding of Trump only to surface transferrin receptors. Therefore, the epitope recognized by Trump is near but not identical to the transferrin binding site. Stimulation of peripheral blood lymphocytes with phytohemagglutinin induced both the OKT9 epitope and the Trump epitope, but 12-phorbol 13 myristate acetate induced only the OKT9 epitope. Growth of some cell lines was inhibited by Trump but not by OKT9. No structural difference was found between transferrin receptor molecules reactive with Trump and those reactive with OKT9. In support of these results, Trump was able to immunoprecipitate transferrin receptor molecules solubilized from low-grade follicular lymphoma cells even though it did not bind to the receptors exposed on the surface of these cells. These findings imply that low-grade lymphoma cells differ from high-grade lymphoma cells not in the structures of their transferrin receptors but in their exposure of the molecule on the cell surface.
Takahashi
S
S
Department of Medicine, Stanford University Medical Center, CA 94305.
Esserman
L
L
Levy
R
R
D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D000939:Epitopes / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D007163:Immunosorbent Techniques; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D010835:Phytohemagglutinins / Q000494:pharmacology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000276:immunology / Q000378:metabolism; D011990:Receptors, Transferrin / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000939:Epitopes; D010835:Phytohemagglutinins; D011990:Receptors, Transferrin; D014168:Transferrin; D013755:Tetradecanoylphorbol Acetate