Characterization of CD4+ T Cell Autoreactivity to Self-MHC in New Zealand Hybrid Mice

The New Zealand white (NZW) H2z locus is strongly associated with the development of autoimmune disease in (NZB × NZW)F1 mice, a model of systemic lupus erythematosus. To better understand the role of H2z in autoimmunity, we generated CD4+ T cell hybridomas from the spleen and lymph nodes of unimmunized (NZB × NZW)F1 mice and characterized their specificity. We found that over 50% of the hybridomas responded to syngeneic (H2d/z) spleen cells in the absence of exogenous antigen. Many of these autoreactive hybridomas responded to spleen cells expressing H2z and used H2z class II (I-Az or I-Ez) molecules for presentation. Interestingly, nearly one third of the H2z-reactive hybridomas could not respond to spleen cells expressing only H2z class II molecules. These studies characterize a frequent population of autoreactive CD4+ T cells in lupus mice and indicate that major histocompatibility complex molecules in addition to class II may be important for this self-recognition.