PMID- 28832583
OWN - NLM
STAT- MEDLINE
DCOM- 20170918
LR  - 20210103
IS  - 1553-7358 (Electronic)
IS  - 1553-734X (Print)
IS  - 1553-734X (Linking)
VI  - 13
IP  - 8
DP  - 2017 Aug
TI  - Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions 
      and identifies allostery regulating HLA specificity.
PG  - e1005725
LID - 10.1371/journal.pcbi.1005725 [doi]
LID - e1005725
AB  - The precise identification of Human Leukocyte Antigen class I (HLA-I) binding 
      motifs plays a central role in our ability to understand and predict 
      (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting 
      co-occurrence of HLA-I alleles across ten newly generated as well as forty public 
      HLA peptidomics datasets comprising more than 115,000 unique peptides, we show 
      that we can rapidly and accurately identify many HLA-I binding motifs and map 
      them to their corresponding alleles without any a priori knowledge of HLA-I 
      binding specificity. Our approach recapitulates and refines known motifs for 43 
      of the most frequent alleles, uncovers new motifs for 9 alleles that up to now 
      had less than five known ligands and provides a scalable framework to incorporate 
      additional HLA peptidomics studies in the future. The refined motifs improve 
      neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA 
      peptidomics data are ideal for in silico predictions of neo-antigens from tumor 
      exome sequencing data. The new motifs further reveal distant modulation of the 
      binding specificity at P2 for some HLA-I alleles by residues in the HLA-I binding 
      site but outside of the B-pocket and we unravel the underlying mechanisms by 
      protein structure analysis, mutagenesis and in vitro binding assays.
FAU - Bassani-Sternberg, Michal
AU  - Bassani-Sternberg M
AUID- ORCID: 0000-0002-1934-954X
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Chong, Chloe
AU  - Chong C
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Guillaume, Philippe
AU  - Guillaume P
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Solleder, Marthe
AU  - Solleder M
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
FAU - Pak, HuiSong
AU  - Pak H
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Gannon, Philippe O
AU  - Gannon PO
AUID- ORCID: 0000-0003-3263-3999
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Kandalaft, Lana E
AU  - Kandalaft LE
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Coukos, George
AU  - Coukos G
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
FAU - Gfeller, David
AU  - Gfeller D
AUID- ORCID: 0000-0002-3952-0930
AD  - Ludwig Centre for Cancer Research, University of Lausanne, Epalinges, 
      Switzerland.
AD  - Department of Fundamental Oncology, University Hospital of Lausanne, Lausanne, 
      Switzerland.
AD  - Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
LA  - eng
PT  - Journal Article
DEP - 20170823
PL  - United States
TA  - PLoS Comput Biol
JT  - PLoS computational biology
JID - 101238922
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
SB  - IM
MH  - Amino Acid Motifs/*genetics
MH  - Binding Sites/genetics
MH  - Histocompatibility Antigens Class I/*chemistry/genetics/metabolism
MH  - Humans
MH  - Peptides/analysis/*chemistry/genetics/metabolism
MH  - Protein Binding/genetics
MH  - Proteome/*chemistry/genetics/metabolism
MH  - Proteomics/*methods
PMC - PMC5584980
COIS- The authors have declared that no competing interests exist.
EDAT- 2017/08/24 06:00
MHDA- 2017/09/19 06:00
PMCR- 2017/08/01
CRDT- 2017/08/24 06:00
PHST- 2017/04/05 00:00 [received]
PHST- 2017/08/17 00:00 [accepted]
PHST- 2017/09/05 00:00 [revised]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2017/09/19 06:00 [medline]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2017/08/01 00:00 [pmc-release]
AID - PCOMPBIOL-D-17-00555 [pii]
AID - 10.1371/journal.pcbi.1005725 [doi]
PST - epublish
SO  - PLoS Comput Biol. 2017 Aug 23;13(8):e1005725. doi: 10.1371/journal.pcbi.1005725. 
      eCollection 2017 Aug.