anchor side chains of short peptide fragments trigger ligand-exchange of class ii mhc molecules锚侧链的短肽片段引发ligand-exchange二类mhc分子.pdfVIP

Anchor Side Chains of Short Peptide Fragments Trigger Ligand-Exchange of Class II MHC Molecules 1 ¨ 1 2 ¨ 1 1,3 Shashank Gupta , Sabine Hopner , Bernd Rupp , Sebastian Gunther , Katharina Dickhaut , Noopur 1 1 ¨ 2 ¨ 4 ¨ 4 1 Agarwal , M. Cristina Cardoso , Ronald Kuhne , Karl-Heinz Wiesmuller , Gunther Jung , Kirsten Falk *, ¨ 1* Olaf Rotzschke ¨ 1 Max-Delbruck-Center for Molecular Medicine (MDC), Berlin, Germany, 2 Leibniz-Institute for Molecular Pharmacology (FMP), Berlin, Germany, 3 Charite Berlin, Berlin, ¨ ¨ Germany, 4 University of Tubingen, Tubingen, Germany Abstract Class II MHC molecules display peptides on the cell surface for the surveillance by CD4+ T cells. To ensure that these ligands accurately reflect the content of the intracellular MHC loading compartment, a complex processing pathway has evolved that delivers only stable peptide/MHC complexes to the surface. As additional safeguard, MHC molecules quickly acquire a ‘non-receptive’ state once they have lost their ligand. Here we show now that amino acid side chains of short peptides can bypass these safety mechanisms by triggering the reversible ligand-exchange. The catalytic activity of dipeptides such as Tyr-Arg was stereo-specific and could be enhanced by modifications addressing the conserved H-bond network near the P1 pocket of the MHC molecule. It affected both antigen-loading and ligand-release and strictly correlated with reported anchor preferences of P1, th