Demonstration of the requirement for self antigen in the activation of autoreactive T cells.

An HLA-DR4-restricted T cell clone (26G11), which was reactive to autologous non-T cells without any nominal antigens, was established from an unimmunized normal subject that was DR1/4 positive. The reactivity of the clone was examined against L cells (LDR4) transfected with the particular DR4 genes obtained from the same subject. 26G11 cells proliferated slightly in response to LDR4 cells, but the proliferation was markedly augmented by the addition of cell lysate from an autologous B cell line. In addition, 26G11 cells killed LRD4 cells sensitized by preincubation with the cell lysate more efficiently than LDR4 cells without treatment. When LDR4 cells were preincubated with cell lysate from allogenic B cell lines, effective killing of the target cells by clone 26G11 was also observed. These data strongly suggest that this autoreactive T cell clone (26G11) recognizes endogenous antigen in the context of the DR4 molecule. This directly demonstrates the requirement for self antigen in the activation of human autoreactive T cells from a normal subject.