AUTOIMMUNE DIABETES-PRONE NOD MICE EXPRESS THE LYT2(ALPHA) (LYT2.1) AND LYT3(ALPHA) (LYT3.1) ALLELES OF CD8

Predisposition to Type I insulin-dependent diabetes (IDD) has a strong underlying genetic basis involving class II major histocompatibility complex (MHC) genes as well as several non-MHC genetic systems. In the non-obese diabetic (NOD) mouse, a model for human IDD, genes associat ed with the appearance of immune cell infiltrates in the pancreatic is lets (insulitis) and/or overt IDD have been mapped to chromosomes 1, 3 , 6, 11, and 17. A recent report has suggested that CD8(+) lymphocytes of the NOD mouse might be deficient in the expression of the CD8 beta molecule, a protein encoded by a gene on chromosome 6. The CD8 beta m olecule is a T-cell surface marker, the lack of which could affect sel ection in the thymus, possibly permitting autoreactive T-cell clones t o populate the peripheral lymphoid tissues. For this reason, we examin ed the expression of the CD8 molecule by lymphocytes in the NOD mouse. Results indicate that the NOD mouse is not deficient in its transcrip tion of detectable mRNA encoding either the CD8 alpha or beta subunits . However, the NOD mouse expresses the Lyt2a and Lyt3a alleles, sugges ting that a portion of chromosome 6 centromeric to the diabetes-suscep tibility genetic region is derived from an ancestry common to AKR and, like AKR, the CD8 alpha and CD8 beta 3.1 (but not CD8 beta 3.2) subun its are detected on the cell surface of T lymphocytes of the NOD mouse . Interestingly, though, the CD8 beta 3.1 molecule may not be expresse d in the NOD mouse to the same extent as it is expressed in the AKR/J mouse, suggesting the possibility that the NOD mouse possesses a defec t somewhere between transcription and cell surface expression of the C D8 beta molecule.