Autoreactivity of T cells from nonobese diabetic mice: An I-A(g7)-dependent reaction

Mice bearing the I-A(g7) class II major histocompatibility complex molecules contain a high number of spontaneous autoreactive T cells, as estimated by limiting-dilution assays. We found this autoreactivity in various strains that bear the I-A(g7) molecule, such as the nonobese diabetic (NOD) mouse strain, which spontaneously develops autoimmune diabetes. However, NOD mice strains that do not express the I-A(g7) molecule, but instead express I-A(b), do not have a high incidence of autoreactive T cells. About 15% of the autoreactive T cells also recognize the I-A(g7) molecule expressed in the T2 line, which is defective in the processing of protein antigens. We interpret this to mean that some of the T cells may interact with class II molecules that are either devoid of peptides or contain a limited peptide content. We also find a high component of autoreactivity among antigen-specific T cell clones. These T cell clones proliferate specifically to protein antigens but also have a high level of reactivity to antigen-presenting cells not pulsed with antigen. Thus, the library of T cell receptors in NOD mice is skewed to autoreactivity, which we speculate is based on the weak peptide-binding properties of I-A(g7) molecules.