PMID- 30467419
OWN - NLM
STAT- MEDLINE
DCOM- 20210603
LR  - 20240328
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 17
IP  - 2
DP  - 2020 Feb
TI  - Distinct editing functions of natural HLA-DM allotypes impact antigen 
      presentation and CD4(+) T cell activation.
PG  - 133-142
LID - 10.1038/s41423-018-0181-1 [doi]
AB  - Classical human leukocyte antigen (HLA) molecules of the major histocompatibility 
      class II (MHCII) complex present peptides for the development, surveillance and 
      activation of CD4(+) T cells. The nonclassical MHCII-like protein HLA-DM (DM) 
      catalyzes the exchange and loading of peptides onto MHCII molecules, thereby 
      shaping MHCII immunopeptidomes. Natural variations of DM in both chains of the 
      protein (DMA and DMB) have been hypothesized to impact peptide presentation, but 
      no evidence for altered function has been reported. Here we define the presence 
      of DM allotypes in human populations covered by the 1000 Genomes Project and 
      probe their activity. The functional properties of several allotypes are 
      investigated and show strong enhancement of peptide-induced T cell activation for 
      a particular combination of DMA and DMB. Biochemical evidence suggests a broader 
      pH activity profile for the new variant relative to that of the most commonly 
      expressed DM allotype. Immunopeptidome analysis indicates that the compartmental 
      activity of the new DM heterodimer extends beyond the late endosome and suggests 
      that the natural variation of DM has profound effects on adaptive immunity when 
      antigens bypass the canonical processing pathway.
FAU - Alvaro-Benito, Miguel
AU  - Alvaro-Benito M
AUID- ORCID: 0000-0002-6019-3567
AD  - Laboratory of Protein Biochemistry, Department of Biology, Chemistry and 
      Pharmacy, Freie Universitat Berlin, Thielallee 63, 14195, Berlin, Germany. 
      malvaro@zedat.fu-berlin.de.
FAU - Morrison, Eliot
AU  - Morrison E
AD  - Laboratory of Protein Biochemistry, Department of Biology, Chemistry and 
      Pharmacy, Freie Universitat Berlin, Thielallee 63, 14195, Berlin, Germany.
FAU - Ebner, Friederike
AU  - Ebner F
AD  - Institut fur Immunologie, Department of Veterinary Medicine, Freie Universitat 
      Berlin, Robert-von-Ostertag-Str. 7-13, 14163, Berlin, Germany.
FAU - Abualrous, Esam T
AU  - Abualrous ET
AD  - Computational Molecular Biology Group, Institute for Mathematics, Freie 
      Universitat Berlin, Berlin, Germany.
FAU - Urbicht, Marie
AU  - Urbicht M
AD  - Laboratory of Protein Biochemistry, Department of Biology, Chemistry and 
      Pharmacy, Freie Universitat Berlin, Thielallee 63, 14195, Berlin, Germany.
FAU - Wieczorek, Marek
AU  - Wieczorek M
AD  - Laboratory of Protein Biochemistry, Department of Biology, Chemistry and 
      Pharmacy, Freie Universitat Berlin, Thielallee 63, 14195, Berlin, Germany.
FAU - Freund, Christian
AU  - Freund C
AD  - Laboratory of Protein Biochemistry, Department of Biology, Chemistry and 
      Pharmacy, Freie Universitat Berlin, Thielallee 63, 14195, Berlin, Germany. 
      chfreund@zedat.fu-berlin.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20181122
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-D Antigens)
RN  - 0 (HLA-DM antigens)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
SB  - IM
MH  - *Alleles
MH  - Antigen Presentation/*genetics
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Databases, Genetic
MH  - Epitopes, T-Lymphocyte/immunology
MH  - HEK293 Cells
MH  - HLA-D Antigens/chemistry/*genetics/immunology
MH  - Haplotypes
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Linkage Disequilibrium
MH  - Lymphocyte Activation/*genetics
MH  - Peptides/immunology
MH  - Polymorphism, Single Nucleotide
MH  - Protein Binding
MH  - Protein Multimerization
MH  - Proteome/immunology
MH  - Proteomics/methods
MH  - Transduction, Genetic
PMC - PMC7000412
OTO - NOTNLM
OT  - Epitope selection
OT  - HLA-DM, Peptide editing
OT  - Immunopeptidome
OT  - Limited polymorphism
OT  - MHC class II
COIS- The authors declare no competing interests.
EDAT- 2018/11/24 06:00
MHDA- 2021/06/04 06:00
PMCR- 2021/02/01
CRDT- 2018/11/24 06:00
PHST- 2018/09/18 00:00 [received]
PHST- 2018/10/16 00:00 [accepted]
PHST- 2018/11/24 06:00 [pubmed]
PHST- 2021/06/04 06:00 [medline]
PHST- 2018/11/24 06:00 [entrez]
PHST- 2021/02/01 00:00 [pmc-release]
AID - 10.1038/s41423-018-0181-1 [pii]
AID - 181 [pii]
AID - 10.1038/s41423-018-0181-1 [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2020 Feb;17(2):133-142. doi: 10.1038/s41423-018-0181-1. Epub 
      2018 Nov 22.