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.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001798:Blood Proteins / Q000276:immunology; D002417:Cattle; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D001324:Autoantigens; D001798:Blood Proteins; D000939:Epitopes; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II