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Unique Epitopes of Common Acute Lymphoblastic Leukemia Antigen Detected by New Monoclonal Antibodies¹

Departments of Molecular Immunology [H. M., Y. H., T. F., B. K. S.] and Pathology [M. P. B.], Roswell Park Memorial Institute,^,3 Buffalo, New York 14263

In the present study we have generated four new monoclonal antibodies (mAbs), termed SN5, SN5a, SN5b, and SN5c, which are directed toward the human common acute lymphoblastic leukemia antigen (CALLA). SN5 and SN5c were generated separately by immunizing two mice with a leukemia antigen preparation isolated from uncultured non-T-/non-B- acute lymphoblastic leukemia cells whereas SN5a and SN5b were generated by immunizing a third mouse with intact KM-3 (a cultured non-T-/non-B- acute lymphoblastic leukemia cell line) cells. It was found that the binding activities of mAbs SN5 and SN5c generated by using an isolated leukemia antigen preparation were approximately twice as large as those of mAbs SN5a and SN5b generated by using intact leukemia cells. All four of the present mAbs induced antigenic modulation of CALLA on the leukemia cells in vitro; subclasses of mAbs appear to be an important factor which influences the kinetics of antigenic modulation. SN5, SN5a, and SN5c immunoprecipitated a distinct M_r 100,000 component from detergent-solubilized cell membrane antigens but SN5b failed to do so. These four mAbs together with J5, another anti-CALLA mAb, were individually tested in a solid phase radioimmunoassay for reactivity with the detergent extracts of various human tissues, i.e., kidney, lymph node, spleen, brain, liver, pancreas, lung, and heart. SN5, SN5a, SN5c, and J5 showed reaction only with kidney, whereas SN5b did not show significant reaction with any tissues including kidney. However, SN5b as well as SN5 showed a significant reaction with kidney in an immunoperoxidase-staining test. These results indicate that the interaction of SN5b with a unique epitope on the CALLA molecule is strongly disturbed by relatively mild detergents (deoxycholate, taurocholate, and Nonidet P-40). These detergents did not significantly disturb the reaction between other mAbs (SN5, SN5a, and SN5c) and the corresponding epitopes on the CALLA molecule. Competitive binding experiments show that the three epitopes recognized by SN5, SN5b, and SN5c are sufficiently close to each other to allow complete or nearly complete reciprocal inhibition of binding to CALLA present on leukemia cells. Peculiar inhibition patterns, however, were observed between SN5a and the other three mAbs. SN5, SN5b, and SN5c inhibited only partially the subsequent binding of SN5a to the leukemia cells. Conversely, SN5a inhibited nearly fully the subsequent bindings of SN5, SN5b, and SN5c. These results suggest another unique epitope defined by SN5a. Based on the present observations, we propose a model illustrating a possible topographic relationship among SN5, SN5a, SN5b, and SN5c epitopes on the CALLA molecule.

¹ This work was supported by USPHS Grants CA19304 and CA37131, awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

³ A unit of the New York State Department of Health.

Received 9/ 2/86. Revised 12/ 3/86. Accepted 1/21/87.

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