PMID- 32010139
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20201116
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 10
DP  - 2019
TI  - Protective Allele for Multiple Sclerosis HLA-DRB1*01:01 Provides Kinetic 
      Discrimination of Myelin and Exogenous Antigenic Peptides.
PG  - 3088
LID - 10.3389/fimmu.2019.03088 [doi]
LID - 3088
AB  - Risk of the development of multiple sclerosis (MS) is known to be increased in 
      individuals bearing distinct class II human leukocyte antigen (HLA) variants, 
      whereas some of them may have a protective effect. Here we analyzed distribution 
      of a highly polymorphous HLA-DRB1 locus in more than one thousand 
      relapsing-remitting MS patients and healthy individuals of Russian ethnicity. 
      Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, 
      whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. 
      Analysis of genotypes revealed the compensatory effect of risk and resistance 
      alleles in trans. We have identified previously unknown MBP(153-161) peptide 
      located at the C-terminus of MBP protein and MBP(90-98) peptide that bound to 
      recombinant HLA-DRB1*01:01 protein with affinity comparable to that of classical 
      antigenic peptide 306-318 from the hemagglutinin (HA) of the influenza virus 
      demonstrating the ability of HLA-DRB1*01:01 to present newly identified 
      MBP(153-161) and MBP(90-98) peptides. Measurements of kinetic parameters of MBP 
      and HA peptides binding to HLA-DRB1*01:01 catalyzed by HLA-DM revealed a 
      significantly lower rate of CLIP exchange for MBP(153-161) and MBP(90-98) 
      peptides as opposed to HA peptide. Analysis of the binding of chimeric MBP-HA 
      peptides demonstrated that the observed difference between MBP(153-161), 
      MBP(90-98), and HA peptide epitopes is caused by the lack of anchor residues in 
      the C-terminal part of the MBP peptides resulting in a moderate occupation of 
      P6/7 and P9 pockets of HLA-DRB1*01:01 by MBP(153-161) and MBP(90-98) peptides in 
      contrast to HA(308-316) peptide. This leads to the P1 and P4 docking failure and 
      rapid peptide dissociation and release of empty HLA-DM-HLA-DR complex. We would 
      like to propose that protective properties of the HLA-DRB1*01 allele could be 
      directly linked to the ability of HLA-DRB1*01:01 to kinetically discriminate 
      between antigenic exogenous peptides and endogenous MBP derived peptides.
CI  - Copyright (c) 2020 Mamedov, Vorobyeva, Filimonova, Zakharova, Kiselev, Bashinskaya, 
      Baulina, Boyko, Favorov, Kulakova, Ziganshin, Smirnov, Poroshina, Shilovskiy, 
      Khaitov, Sykulev, Favorova, Vlassov, Gabibov and Belogurov.
FAU - Mamedov, Azad
AU  - Mamedov A
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Vorobyeva, Nadezhda
AU  - Vorobyeva N
AD  - Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
FAU - Filimonova, Ioanna
AU  - Filimonova I
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Zakharova, Maria
AU  - Zakharova M
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Kiselev, Ivan
AU  - Kiselev I
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Bashinskaya, Vitalina
AU  - Bashinskaya V
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Baulina, Natalia
AU  - Baulina N
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Boyko, Alexey
AU  - Boyko A
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
AD  - Neuroimmunological Department of the Federal Center of Cerebrovascular Diseases 
      and Stroke, Moscow, Russia.
FAU - Favorov, Alexander
AU  - Favorov A
AD  - Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University, 
      Baltimore, MD, United States.
AD  - Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, 
      Russia.
FAU - Kulakova, Olga
AU  - Kulakova O
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Ziganshin, Rustam
AU  - Ziganshin R
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
FAU - Smirnov, Ivan
AU  - Smirnov I
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
AD  - Institute of Fundamental Medicine and Biology, Kazan (Volga) Federal University, 
      Kazan, Russia.
FAU - Poroshina, Alina
AU  - Poroshina A
AD  - National Research Center Institute of Immunology FMBA of Russia, Moscow, Russia.
FAU - Shilovskiy, Igor
AU  - Shilovskiy I
AD  - National Research Center Institute of Immunology FMBA of Russia, Moscow, Russia.
FAU - Khaitov, Musa
AU  - Khaitov M
AD  - National Research Center Institute of Immunology FMBA of Russia, Moscow, Russia.
FAU - Sykulev, Yuri
AU  - Sykulev Y
AD  - Department of Microbiology, Thomas Jefferson University, Philadelphia, PA, United 
      States.
FAU - Favorova, Olga
AU  - Favorova O
AD  - Pirogov Russian National Research Medical University, Moscow, Russia.
FAU - Vlassov, Valentin
AU  - Vlassov V
AD  - Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of 
      Russian Academy of Sciences, Novosibirsk, Russia.
FAU - Gabibov, Alexander
AU  - Gabibov A
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
AD  - Department of Fundamental Medicine, Lomonosov Moscow State University, Moscow, 
      Russia.
FAU - Belogurov, Alexey Jr
AU  - Belogurov A Jr
AD  - Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of 
      Sciences, Moscow, Russia.
AD  - Department of Fundamental Medicine, Lomonosov Moscow State University, Moscow, 
      Russia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200117
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Amino Acids)
RN  - 0 (Antigens)
RN  - 0 (Epitopes)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Myelin Basic Protein)
RN  - 0 (Peptides)
SB  - IM
MH  - Adult
MH  - *Alleles
MH  - Amino Acids/chemistry
MH  - Antigens/chemistry/*immunology
MH  - Chromatography, Liquid
MH  - *Disease Susceptibility
MH  - Epitopes/chemistry/immunology
MH  - Female
MH  - HLA-DRB1 Chains/chemistry/*genetics
MH  - Humans
MH  - Male
MH  - Mass Spectrometry
MH  - Middle Aged
MH  - Multiple Sclerosis/*etiology/metabolism
MH  - Myelin Basic Protein/metabolism
MH  - Myelin Sheath/*metabolism
MH  - Peptides/chemistry/*immunology
MH  - Thermodynamics
PMC - PMC6978714
OTO - NOTNLM
OT  - epitope library
OT  - genetic predisposition to disease
OT  - hemagglutinin
OT  - human leukocyte antigen
OT  - multiple sclerosis
OT  - myelin basic protein
OT  - protective allele
EDAT- 2020/02/06 06:00
MHDA- 2020/11/18 06:00
PMCR- 2019/01/01
CRDT- 2020/02/04 06:00
PHST- 2018/05/18 00:00 [received]
PHST- 2019/12/17 00:00 [accepted]
PHST- 2020/02/04 06:00 [entrez]
PHST- 2020/02/06 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2019.03088 [doi]
PST - epublish
SO  - Front Immunol. 2020 Jan 17;10:3088. doi: 10.3389/fimmu.2019.03088. eCollection 
      2019.