PMID- 24616531
OWN - NLM
STAT- MEDLINE
DCOM- 20140617
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 111
IP  - 12
DP  - 2014 Mar 25
TI  - Expanding the detectable HLA peptide repertoire using 
      electron-transfer/higher-energy collision dissociation (EThcD).
PG  - 4507-12
LID - 10.1073/pnas.1321458111 [doi]
AB  - The identification of peptides presented by human leukocyte antigen (HLA) class I 
      is tremendously important for the understanding of antigen presentation 
      mechanisms under healthy or diseased conditions. Currently, mass 
      spectrometry-based methods represent the best methodology for the identification 
      of HLA class I-associated peptides. However, the HLA class I peptide repertoire 
      remains largely unexplored because the variable nature of endogenous peptides 
      represents difficulties in conventional peptide fragmentation technology. Here, 
      we substantially enhanced (about threefold) the identification success rate of 
      peptides presented by HLA class I using combined electron-transfer/higher-energy 
      collision dissociation (EThcD), reporting over 12,000 high-confident (false 
      discovery rate <1%) peptides from a single human B-cell line. The direct 
      importance of such an unprecedented large dataset is highlighted by the discovery 
      of unique features in antigen presentation. The observation that a substantial 
      part of proteins is sampled across different HLA alleles, and the common 
      occurrence of HLA class I nested sets, suggest that the constraints of HLA class 
      I to comprehensively present the health states of cells are not as tight as 
      previously thought. Our dataset contains a substantial set of peptides bearing a 
      variety of posttranslational modifications presented with marked allele-specific 
      differences. We propose that EThcD should become the method of choice in 
      analyzing HLA class I-presented peptides.
FAU - Mommen, Geert P M
AU  - Mommen GP
AD  - Formulation and Analytical Research, Institute for Translational Vaccinology, 
      3721 MA, Bilthoven, The Netherlands.
FAU - Frese, Christian K
AU  - Frese CK
FAU - Meiring, Hugo D
AU  - Meiring HD
FAU - van Gaans-van den Brink, Jacqueline
AU  - van Gaans-van den Brink J
FAU - de Jong, Ad P J M
AU  - de Jong AP
FAU - van Els, Cecile A C M
AU  - van Els CA
FAU - Heck, Albert J R
AU  - Heck AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140310
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 (HLA Antigens)
RN  - 0 (Peptides)
SB  - IM
MH  - Alleles
MH  - B-Lymphocytes/immunology
MH  - Cell Line
MH  - Chromatography, Liquid
MH  - Electron Transport
MH  - HLA Antigens/*chemistry/genetics/immunology
MH  - Humans
MH  - Peptides/*chemistry/immunology
MH  - Tandem Mass Spectrometry
PMC - PMC3970485
OTO - NOTNLM
OT  - binding motif
OT  - electron-transfer dissociation
OT  - human leukocyte antigen class I
OT  - major histocompatibility complex
OT  - phosphorylation
COIS- The authors declare no conflict of interest.
EDAT- 2014/03/13 06:00
MHDA- 2014/06/18 06:00
PMCR- 2014/09/25
CRDT- 2014/03/12 06:00
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2014/06/18 06:00 [medline]
PHST- 2014/09/25 00:00 [pmc-release]
AID - 1321458111 [pii]
AID - 201321458 [pii]
AID - 10.1073/pnas.1321458111 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2014 Mar 25;111(12):4507-12. doi: 
      10.1073/pnas.1321458111. Epub 2014 Mar 10.