AUTHOR CONTACT:
Cynthia E. Dunbar
NIH, National Heart, Lung and Blood Institute, Bethesda, MD USA
Phone: 301-496-1434; Fax: 301-496-8396; E-mail: dunbarc@nhlbi.nih.gov
View the PDF of this article at: https://www.the-jci.org/article.php?id=26041
IMMUNOLOGY
Navigating Type I Diabetes with a now accurate epitope map
For many years, people have tried to determine the particular peptide epitopes of foreign or self-antigens that are presented by a particular MHC class II allele. Thus, scanning for predicted binding motifs, and using phage libraries, have been used in binding assays to identify those peptide epitopes which might be of functional importance in the immune response to foreign antigens and proteins, or the immune response to self antigens in autoimmunity. Unfortunately, despite a number of studies showing that not all of these predictions are borne out, many laboratories have persisted in this method of identifying peptide epitopes.
In a new study appearing on August 1 in The Journal of Clinical Investigation, Emil Unanue and colleagues from Harvard find that 2 molecules, which are the principal molecules which mediate susceptibility to type I diabetes in man (DQ 8) and in the NOD mouse (I-Ag7) have similar function and sequence specificity.
The authors show that when they simply elute from purified DQ8 or I-Ag7 molecules isolated from transfected cells, the peptide epitopes are different from those predicted by other methods. This is important because it shows that prediction is not adequate for determining peptide epitopes seen by immune T cells in various disease states.
In an accompanying commentary, Hidde Ploegh writes, "the comprehensive data set presented h
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Journal of Clinical Investigation
1-Aug-2005