PMID- 19196958
OWN - NLM
STAT- MEDLINE
DCOM- 20090406
LR  - 20240416
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 106
IP  - 8
DP  - 2009 Feb 24
TI  - Phosphorylated self-peptides alter human leukocyte antigen class I-restricted 
      antigen presentation and generate tumor-specific epitopes.
PG  - 2776-81
LID - 10.1073/pnas.0812901106 [doi]
AB  - 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 stabilized 
      the HLA peptide complex in an epitope-specific manner and was observed to exhibit 
      discrete flexibility within the antigen-binding cleft. Collectively, our data 
      suggest that phosphorylation generates neoepitopes that represent demanding 
      targets for T-cell receptor ligation. These findings provide insights into the 
      mode of phosphopeptide presentation by HLA as well as providing a platform for 
      the rational design of a generation of posttranslationally modified tumor 
      vaccines.
FAU - Petersen, Jan
AU  - Petersen J
AD  - Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, 
      School of Biomedical Sciences, Monash University, Victoria 3800, Australia.
FAU - Wurzbacher, Stephanie J
AU  - Wurzbacher SJ
FAU - Williamson, Nicholas A
AU  - Williamson NA
FAU - Ramarathinam, Sri H
AU  - Ramarathinam SH
FAU - Reid, Hugh H
AU  - Reid HH
FAU - Nair, Ashish K N
AU  - Nair AK
FAU - Zhao, Anne Y
AU  - Zhao AY
FAU - Nastovska, Roza
AU  - Nastovska R
FAU - Rudge, Geordie
AU  - Rudge G
FAU - Rossjohn, Jamie
AU  - Rossjohn J
FAU - Purcell, Anthony W
AU  - Purcell AW
LA  - eng
SI  - PDB/3FQN
SI  - PDB/3FQR
SI  - PDB/3FQT
SI  - PDB/3FQU
SI  - PDB/3FQW
SI  - PDB/3FQX
GR  - R01 GM057428/GM/NIGMS NIH HHS/United States
GR  - GM057428-06/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090205
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Epitopes)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
SB  - IM
MH  - Amino Acid Sequence
MH  - Crystallography, X-Ray
MH  - Epitopes/*immunology
MH  - Histocompatibility Antigens Class I/*immunology
MH  - Humans
MH  - Peptides/chemistry/immunology/*metabolism
MH  - Phosphorylation
MH  - Protein Conformation
PMC - PMC2650342
COIS- The authors declare no conflict of interest.
EDAT- 2009/02/07 09:00
MHDA- 2009/04/07 09:00
PMCR- 2009/08/24
CRDT- 2009/02/07 09:00
PHST- 2009/02/07 09:00 [entrez]
PHST- 2009/02/07 09:00 [pubmed]
PHST- 2009/04/07 09:00 [medline]
PHST- 2009/08/24 00:00 [pmc-release]
AID - 0812901106 [pii]
AID - 6693 [pii]
AID - 10.1073/pnas.0812901106 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2776-81. doi: 
      10.1073/pnas.0812901106. Epub 2009 Feb 5.