Dendritic cells purified from myeloma are primed with tumor-specific antigen (idiotype) and activate CD4(+) T cells

Multiple myelomas produce tumor-specific antigen (TSA) in the form of idiot ype (Id) on monoclonal 1g. CD4(+) T cells can recognize Id-peptide on MHC c lass II molecules and protect against challenges with MOPC315 cells, which are, as common for myelomas, class Ii-negative. The present study explains these previous results by demonstrating that Id can be transferred from mye loma cells to antigen-presenting cells (APC), which present processed Id-pe ptide on their class II molecules to Id-specific T cell receptor-transgenic (TCR-TG) CD4(+) T cells. Id-primed tumor APC were heterogeneous, the major ity being dendritic cells with class II+, CD11b(+) CD11c(+) CD40(+) CD80(+) CD86(+) markers. The APC were localized beneath CD31(+) endothelial cells of tumor microvessels, and their frequency declined with tumor progression. The APC could stimulate Id-specific naive TCR-TC, short-term polarized TCR -TG, and cloned CD4(+) T cells to proliferate and produce cytokines in vitr o. Furthermore, small MOPC315 tumors established in Id-specific TCR-TC mice contained clusters of activated (CD69(+)CD25(+)) and proliferating (BrdUrd (+)) Id-specific transgenic CD4(+) blasts. The activated Id-specific T cell s were located adjacent to Id-primed dendritic cells in the tumor. Thus, a TSA can be transferred in vivo from myeloma, and possibly other types of ca ncer cells to APC for MHC class II presentation to CD4(+) T cells.