Dendritic cells internalise and re-present conformationally intact soluble MHC class I alloantigen for generation of alloantibody

Abstract

Following organ transplantation soluble MHC class I is released from the graft and may contribute to alloimmunity. We determined in a well-established rat model whether DC are able to internalise soluble MHC class I alloantigen and then re-present intact alloantigen to B cells and Tcells for generation of an alloantibody or CD8 T cell response. PVG.RT1u BM-derived DC internalised (via an active process) and retained intact a recombinant soluble form of RT1-Aa (sRT1-Aa). When PVG.RTIu rats were immunised with sRT1-Aa-pulsed syngeneic DC they developed a strong anti-sRT1-Aa alloantibody response and showed accelerated rejection of RT1-Aa-disparate PVG.R8 heart grafts. Alloantibody production and accelerated heart graft rejection were both dependent on immunisation with viable sRTI-Aa-pulsed DC. The alloantibody response to sRT1-Aa- pulsed DC was directed exclusively against conformational epitopes expressed by sRT1-Aa and not epitopes expressed, for example, by non-conformational sRT1-Aa heavy chain. Immunisation with sRT1-Aa-pulsed syngeneic DC did not stimulate a CD8 T cell response. Our findings suggest a novel alloantigen recognition pathway whereby soluble MHC class I alloantigen released from an allograft may be taken up by recipient DC and presented in an intact unprocessed form to B cells for the generation of an alloantibody response. © 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.