Parameters involved in the recognition of fresh human leukemic blasts by tumor-specific cytolytic T cell clones: a model study

Although clinical experience and in vitro data provide evidence of an anti- leukemic activity of T cells, there are few examples of recognition of leuk emic cells by tumor-specific T cells in vitro. Tumor antigens encoded by th e MAGE genes are useful tools to study this recognition. We tested the sens itivity to recognition and lysis by anti-MAGE CTL clones of MAGE-A1 positiv e cell lines HL60 and K562, after transfection with an HLA-A1 construct, an d of fresh leukemic blasts from 10 HLA-A2 patients, after incubation with a peptide encoded by gene MAGE-A3. The presentation of MAGE antigens by leuk emic cell lines and fresh leukemic blasts induced TNF secretion and cytotox icity by MAGE-specific CD8(+) CTL clones. The amount of peptide presented b y the leukemic blasts, more than the level of expression of HLA class I, ad hesion or costimulatory molecules, was the major limiting factor for recogn ition. These data-indicate that leukemic cells may be targeted by T cells s howing specificity for a leukemia antigen. (C) 2000 Elsevier Science Ltd. A ll rights reserved.