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

Carla J. Aldrich, Taehoon Chun, H Rex Gaskins, Evan Hermel

Research output: Contribution to journalArticle

Abstract

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-1b, (encoded by H2-T23b) 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-1b binds a nonamer peptide derived from the leader sequence of preproinsulin II. Alloreactive anti-Qa-1b CTL lyse Qa-1 plus insulin peptide bearing cells. Blocking assays further demonstrate that this peptide binds in the peptide binding cleft of Qa-1b. DNA sequencing of Qa-1 from the NOD (non obese diabetic, H-2g7) mouse shows that this strain expresses Qa-1a. 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-1a CTL, whereas anti-Qa-1b 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.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998

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ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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