TY - JOUR
T1 - Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice
AU - Latek, Robert R.
AU - Suri, Anish
AU - Petzold, Shirley J.
AU - Nelson, Christopher A.
AU - Kanagawa, Osami
AU - Unanue, Emil R.
AU - Fremont, Daved H.
N1 - Funding Information:
We are grateful to the Kilo Research Foundation, Burroughs-Wellcome Foundation, National Institutes of Health, and Washington University–Monsanto Agreement for their continuous support of our research. We would like to express our appreciation to Dr. Ian Wilson for helpful discussions and to Dr. John Kappler for his generosity with reagents. Our gratitude goes to Barb Vaupel for her molecular biology expertise, Michael Miley for assistance with manuscript figures, and Kyunghee Choi for encouragement and support.
PY - 2000
Y1 - 2000
N2 - We have determined the crystal structure of I-A(g)7, an integral component in murine type I diabetes development. Several features distinguish I-A(g)7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-A(g)7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-A(g)7 epitope HEL(11-25) support a comprehensive structure-based I-A(g)7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-A(g)7 in autoimmunity.
AB - We have determined the crystal structure of I-A(g)7, an integral component in murine type I diabetes development. Several features distinguish I-A(g)7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-A(g)7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-A(g)7 epitope HEL(11-25) support a comprehensive structure-based I-A(g)7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-A(g)7 in autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=0033662436&partnerID=8YFLogxK
U2 - 10.1016/S1074-7613(00)80220-4
DO - 10.1016/S1074-7613(00)80220-4
M3 - Article
C2 - 10894169
AN - SCOPUS:0033662436
SN - 1074-7613
VL - 12
SP - 699
EP - 710
JO - Immunity
JF - Immunity
IS - 6
ER -