Tumor-specific recognition of human myeloma cells by idiotype-induced CD8(+) T cells.
Journal Article (Journal Article)
Immunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein-specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1-type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell-mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether 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 autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer-sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I-restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response. (Blood. 2000;96:2828-2833)
Full Text
Duke Authors
Cited Authors
- Li, Y; Bendandi, M; Deng, Y; Dunbar, C; Munshi, N; Jagannath, S; Kwak, LW; Lyerly, HK
Published Date
- October 15, 2000
Published In
Volume / Issue
- 96 / 8
Start / End Page
- 2828 - 2833
PubMed ID
- 11023518
International Standard Serial Number (ISSN)
- 0006-4971
Language
- eng
Conference Location
- United States