Characterization of CD4(+) T cell autoreactivity to self-MHC in New Zealand hybrid mice

The New Zealand white (NZW) H2(z) locus is strongly associated with the dev elopment of autoimmune disease in (NZB x NZW)F-1 mice, a model of systemic lupus erythematosus, To better understand the role of H2(z) in autoimmunity , we generated CD4(+) T cell hybridomas from the spleen and lymph nodes of unimmunized (NZB x NZW)F-1 mice and characterized their specificity. We fou nd that over 50% of the hybridomas responded to syngeneic (H2(d/z)) spleen cells in the absence of exogenous antigen. Many of these autoreactive hybri domas responded to spleen cells expressing H2(z) and used H2(z) class II (I -A(z) or I-E-z) molecules for presentation. Interestingly, nearly one third of the H2(z)-reactive hybridomas could not respond to spleen cells express ing only H2(z) class II molecules. These studies characterize a frequent po pulation of autoreactive CD4(+) T cells in lupus mice and indicate that maj or histocompatibility complex molecules in addition to class II may be impo rtant for this self-recognition. (C) 2000 Academic Press.