MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions

Presentation of antigen to T cells is generally restricted by MHC type but the mixed leukocyte reaction (MLR) was thought to involve direct stimulatio n by dendritic cells (DC) of allogeneic T cells. However, here we showed th at DC bearing allogeneic MHC class Il acted synergistically with responder- type DC. Removal of residual DC from 'purified' responder T cell population s was achieved using treatment with DC-specific antibody and complement. Th ese DC-depleted cells showed a significantly reduced response to allogeneic DC which was restored by addition of DC syngeneic with responder T cells. The studies support the concept that a major component of the MLR is the se condary presentation of alloantigens acquired from stimulator DC by DC of r esponder type. To investigate the reasons why DC and not other cells stimul ate an MLR, synergy between DC and other cell types was investigated. Syner gy was found exclusively between DC; macrophages, B cells or L cells transf ected with MHC class II molecules did not contribute. When allogeneic DC we re mixed in culture, transfer of MHC molecules between DC was observed as a ssessed by flow cytometry. Freshly obtained cell-free supernatants from cul tured DC contained MHC class II and stimulated primary allogeneic MLR, Dc o f responder type acquired allogeneic MHC molecules from the supernatants an d stimulated proliferation in syngeneic T cells. The capacity of DC both to shed and to acquire MHC molecules may contribute to their potency in stimu lating primary responses, and could explain why passenger DC within allogra fts provide a potent stimulus for graft rejection.