Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells

Immunoglobulin secreted by myeloma cells contains a unique antigenic determ inant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with my eloma, it is not known whether primary myeloma tumor cells can present natu rally processed Id peptides on their surface as a target. We immunized 2 he althy human stem-cell donors with Id proteins from their recipients. T cell s from the immunized donors released high levels of T-helper 1-type cytokin es in response to stimulation with myeloma cells from their recipients. The T-cell-mediated cytokine response to tumor cells was blocked by a major hi stocompatibility complex (MHC) class I monoclonal antibody, whereas the res ponse to soluble Id protein was dependent on MHC class II. To investigate w hether Id-specific CD8(+) T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologou s dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma c ells was demonstrated by the lack of killing of autologous nonmalignant B c ells or natural killer-sensitive K562 cells. Lysis of autologous myeloma ta rgets was restricted by MHC class I molecules. These data represent the fir st report of class I-restricted T-cell recognition of fresh autologous myel oma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response.(Blood. 2000;96:2828-2833) (C) 20 00 by The American Society of Hematology.