Disabling an integral CTL epitope allows suppression of autoimmune diabetes by intranasal proinsulin peptide
J. Clin. Invest. Nathan R. Martinez, et al. 111:1365 doi:10.1172/JCI17166 [Go to this article.]

Figure 2
Proinsulin B24–C36 peptides bind to I-A^g7. (a) Binding of proinsulin B24–C36 peptides to purified, soluble NOD mouse MHC class II, I-A^g7. Competition between biotinylated HEL 10–23 peptide and unlabeled HEL 10–23 (open squares), proinsulin B24–C36 (filled circles), B23–C33 (open triangles), or B22–C31 (filled diamonds) for binding to I-A^g7 measured by ELISA. (b) Model of B24–C36 bound to I-A^g7 at pH 7.0, viewed from the perspective of the T cell receptor (TCR). Anchor residues at position 1F (p1F) (B24) and p9R (C32) point into the groove of I-A^g7 and are only partially visible. The p4T points into the groove at pocket 4 and is partially visible, as is p6M. By contrast, residues at p2F, p3Y, p5P, p7S, and p8R point upward and are accessible by the TCR. Note the interaction of α75K and α76R with the three acidic residues at the C-terminus of the peptide as shown in the main figure and in the bottom right-hand corner inset. The latter is generated by rotating this segment of the main figure by 40 degrees along the x axis (bottom up, top into the paper) and 20 degrees along the y axis (right up, left into the paper). α75K interacts with the side chain carboxylate (and secondarily the terminal carboxylate) of p13D (C36), while α76R interacts with p10E (C33) and p12E (C35).