CTL recognition of Qa-1^b binding a peptide from preproinsulin leader sequences and characterization of Qa-1 from the NOD mouse

Cytotoxic T lymphocyte (CTL) recognition of major histocompatibility complex (MHC) class I molecules binding peptides is important to the proper functioning of the immune system. Evidence indicates that the MHC class IB molecule Qa-1^b, (encoded by H2-T23^b) presents antigens to αβ and γδ T cells and that lymphocytes restricted to Qa-1 may play a role in immune regulation. We demonstrate that Qa-1^b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1^b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1^b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2^g7) mouse shows that this strain expresses Qa-1^a. However, alloreactive CTL recognition of Qa-1 on NOD cells may be unusually influenced by the available peptide pool. In addition, NIT-1, a pancreatic β cell line derived from the NOD mouse is not recognized by anti-Qa-1^a CTL, whereas anti-Qa-1^b CTL lyse βTC6-F7, a pancreatic line from a normal mouse strain. βTC6 and NIT-1 cells both were killed by anti-H2 class IA CTL. Thus, Qa-1 expression and peptide presentation, particularly on pancreatic β cells may be important in the regulation of autoimmune responses.