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 development 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 found that over 50% of the hybridomas responded to syngeneic (H2(d/z)) spleen cells in the absence of exogenous antigen. Many of these autoreactive hybridomas 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 expressing only H2(z) 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.
Roark
C L
CL
Department of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.
Kotzin
B L
BL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006822:Hybrid Cells / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D008822:Mice, Transgenic; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D000949:Histocompatibility Antigens Class II