The role of foreign antigens in the induction of human AMLR.

We present evidence that most T cells proliferating in response to autologous SRBC-separated NT cells are not specific for autoantigens but for antigens derived from xenogeneic sources. The conclusion was based on the following three observations: First, we found that NT cells isolated in the absence of xenoproteins by means of density gradient centrifugation on Percoll only weakly stimulated autologous T cells. NT cells isolated by the above method in the absence of xenogeneic determinants readily acquired stimulatory capacity after brief exposure to either SRBC or FCS. Secondly, restimulation of T memory cells generated in 1 degree AMLR against SRBC-separated autologous NT cells was exclusively seen when NT cells exposed to or separated with xenoproteins were used for restimulation. Thirdly, T memory cells generated against SRBC-separated autologous NT cells were specifically restimulated by autologous Percoll-separated NT cells which had been pulsed with a variety of xenogeneic mammalian sera. These xenogeneic determinants were preferentially recognized in context with autologous HLA-DR+ cells. From these findings and from our previous results which indicated an absolute requirement of HLA-DR+-adherent NT cells, we conclude that human AMLR primarily does not represent an autoantigen but a xenoantigen response which is genetically restricted by the HLA-DR type of the antigen-presenting cell.