Response of MRL/Mp-+/+ mice to mouse Sm: non-H-2-linked genes determine T cell recognition

In normal mouse strains, the T cell proliferative response to the nuclear autoantigen Sm is under MHC-linked Ir gene control. Autoimmune MRL/Mp-+/+ (+/+) mice, which spontaneously make anti-Sm antibodies, have the nonresponder H-2k MHC genotype, yet their T cells respond to mouse Sm. In the present study, we have used Sm-reactive continuous T cell lines to show that the Sm responsiveness of +/+ T cells is not due to aberrancy of the Iak molecules expressed on +/+ antigen-presenting cells. Additionally, the failure of normal Iak mouse strains to respond to mouse Sm could not be attributed to the influence of suppressor cells. Therefore, the response of +/+ mice to mouse Sm is probably due to the development of an abnormal repertoire of T cells capable of recognizing self-antigens in the context of Ia. Analyses of F1 hybrid and backcross mice indicated that their responsiveness was inherited in a dominant manner, probably as a single gene not linked to H-2. Further investigation of this gene and its mode of action may lead to increased understanding of the mechanisms of spontaneous autoimmunity in SLE mice.