Phosphorylated self-peptides alter human leukocyte antigen class I-restricted antigen presentation and generate tumor-specific epitopes
Jan Petersen, Stephanie J Wurzbacher, Nicholas A Williamson, Sri H Ramarathinam, Hugh H Reid, Ashish KN Nair, Anne Y Zhao, Roza Nastovska, Geordie Rudge, Jamie Rossjohn, Anthony W Purcell
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | NATL ACAD SCIENCES | Published : 2009
Human leukocyte antigen (HLA) class I molecules present a variety of posttranslationally modified epitopes at the cell surface, although the consequences of such presentation remain largely unclear. Phosphorylation plays a critical cellular role, and deregulation in phosphate metabolism is associated with disease, including autoimmunity and tumor immunity. We have solved the high-resolution structures of 3 HLA A2-restricted phosphopeptides associated with tumor immunity and compared them with the structures of their nonphosphorylated counterparts. Phosphorylation of the epitope was observed to affect the structure and mobility of the bound epitope. In addition, the phosphoamino acid stabiliz..View full abstract
Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by National Institutes of Health
A. W. P. is a National Health and Medical Research Council of Australia (NH&MRC) Senior Research Fellow, and J. R. is an Australian Research Council Federation Fellow. This work was supported by NH&MRC Project Grants 491117 and 508927 and National Institutes of Health Grant GM057428-06.