Prevalence of antigen receptor variants in human T cell lines and tumors.
Previously, we have shown that a human T acute lymphoblastic leukemia cell line, HPB-ALL, exhibits clonal heterogeneity within its Ag receptor, as revealed by varying reactivity patterns with a panel of anti-idiotype mAb. We now extend these findings to another human T acute lymphoblastic leukemia cell line, SUP-T13, and to two fresh human chronic lymphocytic leukemias, JE and EF. In the two cell lines, two types of Ag receptor variants could be found: those that retained a receptor molecule but lost reactivity with an anti-idiotype mAb (idiotype variants), and those which had lost surface receptor expression completely (receptor-negative variants). The idiotype variants, at least in HPB-ALL, have differentially glycosylated receptor alpha-chains from the parent. The receptor-negative cells, in HPB-ALL as well as in SUP-T13, produce cytoplasmic receptor and CD3 proteins but do not transport them to the surface. Neither idiotype nor receptor-negative variants could be detected in either of the fresh tumors of chronic lymphocytic leukemias. The limit of sensitivity in these analyses was about 0.05%. We conclude that antigen receptor variants can spontaneously occur in cell lines derived from acute lymphoblastic leukemias, but are infrequent in chronic lymphocytic leukemias in vivo, and that therapy with anti-idiotype mAb may be a viable strategy for these malignancies.
Stanford University Medical School, CA 94305.
H T
HT
Maecker
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Levy
D000818:Animals; D000911:Antibodies, Monoclonal; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis; D011946:Receptors, Antigen / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D012333:RNA, Messenger; D011946:Receptors, Antigen