BBUF rats, derived from BB rats, spontaneously develop a form of insulin-dependent diabetes mellitus (IDDM) associated with infiltration of the islets of Langerhans by lymphocytes (insulitis). BBUF rats bear the RT1U major histocompatibility complex (MHC) haplotype that we have shown to be necessary for the expression of this form of IDDM. A T-lymphocyte line obtained from the pancreas of a diabetic rat (UPCC.5) and three T-lymphocyte hybridomas derived by fusing T-lymphocytes of BBUF rats (MUS1.2, MUS1.13, and MUP3.21) respond to islet cell antigens in an MHC-restricted way. UPCC.5 responds to a combination of islet cell antigens (ICAg) and antigen-presenting cells by proliferation, whereas the T-hybridoma responses are detected on the basisof IL-2 production in a similar assay. This study reveals that an antiserum against μhaplotype MHC antigens or a monoclonal antibody against the product of the D class II subregion of the rat MHC could inhibit ICAg recognition. A monoclonal antibody against the product of the B class II MHC subregion of the rat was not inhibitory. These results suggest that RT1.D antigens (analogous to human DR and mouse I-E) restrict islet cell recognition in this rat model of spontaneous IDDM.

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