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.