PMID- 37085710
OWN - NLM
STAT- MEDLINE
DCOM- 20230425
LR  - 20230512
IS  - 2399-3642 (Electronic)
IS  - 2399-3642 (Linking)
VI  - 6
IP  - 1
DP  - 2023 Apr 21
TI  - Machine learning reveals limited contribution of trans-only encoded variants to 
      the HLA-DQ immunopeptidome.
PG  - 442
LID - 10.1038/s42003-023-04749-7 [doi]
LID - 442
AB  - Human leukocyte antigen (HLA) class II antigen presentation is key for 
      controlling and triggering T cell immune responses. HLA-DQ molecules, which are 
      believed to play a major role in autoimmune diseases, are heterodimers that can 
      be formed as both cis and trans variants depending on whether the alpha- and beta-chains 
      are encoded on the same (cis) or opposite (trans) chromosomes. So far, limited 
      progress has been made for predicting HLA-DQ antigen presentation. In addition, 
      the contribution of trans-only variants (i.e. variants not observed in the 
      population as cis) in shaping the HLA-DQ immunopeptidome remains largely 
      unresolved. Here, we seek to address these issues by integrating state-of-the-art 
      immunoinformatics data mining models with large volumes of high-quality HLA-DQ 
      specific mass spectrometry immunopeptidomics data. The analysis demonstrates 
      highly improved predictive power and molecular coverage for models trained 
      including these novel HLA-DQ data. More importantly, investigating the role of 
      trans-only HLA-DQ variants reveals a limited to no contribution to the overall 
      HLA-DQ immunopeptidome. In conclusion, this study furthers our understanding of 
      HLA-DQ specificities and casts light on the relative role of cis versus 
      trans-only HLA-DQ variants in the HLA class II antigen presentation space. The 
      developed method, NetMHCIIpan-4.2, is available at 
      https://services.healthtech.dtu.dk/services/NetMHCIIpan-4.2 .
CI  - (c) 2023. The Author(s).
FAU - Nilsson, Jonas Birkelund
AU  - Nilsson JB
AUID- ORCID: 0000-0002-1322-2644
AD  - Department of Health Technology, Technical University of Denmark, DK-2800, 
      Lyngby, Denmark.
FAU - Kaabinejadian, Saghar
AU  - Kaabinejadian S
AUID- ORCID: 0000-0002-8434-8703
AD  - Pure MHC, LLC, Oklahoma City, OK, USA.
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, OK, USA.
FAU - Yari, Hooman
AU  - Yari H
AUID- ORCID: 0000-0002-8285-7985
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, OK, USA.
FAU - Peters, Bjoern
AU  - Peters B
AD  - Center for Infectious Disease and Vaccine Research, La Jolla Institute for 
      Immunology, La Jolla, CA, 92037, California, USA.
FAU - Barra, Carolina
AU  - Barra C
AUID- ORCID: 0000-0002-6836-4906
AD  - Department of Health Technology, Technical University of Denmark, DK-2800, 
      Lyngby, Denmark.
FAU - Gragert, Loren
AU  - Gragert L
AUID- ORCID: 0000-0002-5945-6518
AD  - Department of Pathology and Laboratory Medicine, Tulane University School of 
      Medicine, New Orleans, LA, 70112, USA.
FAU - Hildebrand, William
AU  - Hildebrand W
AD  - Department of Microbiology and Immunology, University of Oklahoma Health Sciences 
      Center, Oklahoma City, OK, USA.
FAU - Nielsen, Morten
AU  - Nielsen M
AUID- ORCID: 0000-0001-7885-4311
AD  - Department of Health Technology, Technical University of Denmark, DK-2800, 
      Lyngby, Denmark. morni@dtu.dk.
LA  - eng
GR  - 75N93019C00001/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230421
PL  - England
TA  - Commun Biol
JT  - Communications biology
JID - 101719179
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Humans
MH  - *HLA-DQ Antigens/genetics/chemistry
MH  - HLA Antigens
MH  - *Autoimmune Diseases
MH  - T-Lymphocytes
MH  - Machine Learning
PMC - PMC10121683
COIS- S.K. is an employee at Pure MHC, LLC. The remaining authors declare no competing 
      interests.
EDAT- 2023/04/22 10:42
MHDA- 2023/04/25 10:20
PMCR- 2023/04/21
CRDT- 2023/04/21 23:29
PHST- 2022/10/01 00:00 [received]
PHST- 2023/03/23 00:00 [accepted]
PHST- 2023/04/25 10:20 [medline]
PHST- 2023/04/22 10:42 [pubmed]
PHST- 2023/04/21 23:29 [entrez]
PHST- 2023/04/21 00:00 [pmc-release]
AID - 10.1038/s42003-023-04749-7 [pii]
AID - 4749 [pii]
AID - 10.1038/s42003-023-04749-7 [doi]
PST - epublish
SO  - Commun Biol. 2023 Apr 21;6(1):442. doi: 10.1038/s42003-023-04749-7.