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MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions
P Bedford1, K Garner, S C Knight
1Antigen Presentation Research Group, Imperial College School of Medicine, Northwick Park Institute for Medical Research, Watford Road, Harrow, Middlesex HA1 3UJ, UK.
International Immunology
|November 5, 1999
Summary
Dendritic cells (DC) initiate mixed leukocyte reactions (MLR) by presenting alloantigens. This study reveals that responder-type DC acquire allogeneic MHC molecules from stimulator DC, enabling secondary antigen presentation and T cell proliferation.
Area of Science:
- Immunology
- Cell Biology
Background:
- T cell activation is typically MHC-restricted.
- The mixed leukocyte reaction (MLR) was believed to involve direct allogeneic T cell stimulation by dendritic cells (DC).
Purpose of the Study:
- To investigate the mechanism of T cell stimulation in MLR.
- To determine the role of dendritic cells (DC) in initiating MLR.
- To understand why DC are potent stimulators of MLR.
Main Methods:
- DC depletion from T cell populations using antibody and complement.
- Assessing MLR response after DC depletion and reconstitution.
- Investigating synergy between DC and other antigen-presenting cells.
- Analyzing MHC molecule transfer between DC via flow cytometry.
- Testing the MLR-stimulating capacity of DC supernatants.
Main Results:
- DC-depleted T cells showed reduced allogeneic MLR, restored by syngeneic DC.
- Synergistic MLR stimulation occurred exclusively between DC, not with other cell types.
- Dendritic cells (DC) were observed to transfer MHC molecules to each other.
- Cell-free supernatants from DC contained MHC class II and stimulated primary allogeneic MLR.
- Responder DC acquired allogeneic MHC molecules from supernatants, stimulating syngeneic T cells.
Conclusions:
- A major component of MLR involves secondary presentation of alloantigens by responder-type DC.
- Dendritic cells (DC) shed and acquire MHC molecules, contributing to their potent stimulatory capacity in MLR.
- This mechanism may explain the strong immune response to passenger DC in allografts.