PMID- 35958484
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220813
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 14
IP  - 7
DP  - 2022
TI  - Promoting the formation of Pi-stacking interaction to improve CTL cells 
      activation between modified peptide and HLA.
PG  - 5164-5177
AB  - OBJECTIVE: This study aims to investigate the use of single residue substitution 
      to promote the formation of pi-stacking interactions between peptides and Human 
      leukocyte antigen (HLA)-A*2402 molecules to improve the affinity of peptides and 
      HLA molecules, as well as the level of cytotoxic T lymphocyte (CTL) cells 
      activated by peptides-HLA (p-HLA) complex. METHODS: Molecular docking and 
      molecular dynamics simulation were used to simulate and analyze the interactions 
      and binding free energies between HLA-A*2402-restricted antigen peptides and HLA 
      molecules, before and after the single residue substitution. HLA-A*2402 
      restricted antigen peptides before and after the single residue replacement were 
      loaded into dendritic cells (DCs) in vitro, and further Enzyme-Linked ImmunoSpot 
      (ELispot) test was carried out to evaluate the effect of modified antigen 
      peptides on the immune activation of CTL cells. RESULT: After replacing the 
      antigen peptides with a single residue, some of them could promote the formation 
      of pi-stacking interaction. The binding free energy between the modified antigen 
      peptides and HLA-A*2402, as well as the level of immune activation of CTL cells 
      were mostly higher than before, especially after the replacement of the 9th 
      residue of the polypeptide, such as C9F and C9W. There was a significant negative 
      correlation between the level of activated CTL cells by modified antigen peptides 
      and the total interaction amount of hydrogen bonds and salt bridges. CONCLUSION: 
      Promoting the formation of pi-stacking interaction between antigen peptides and 
      HLA-A*2402 molecules could increase the total binding free energy of p-HLA 
      complex and the level of CTL cells activation. In addition, the amount of 
      hydrogen bonds and salt bridges between peptides and HLA could reduce the level 
      of immune activation. All the characteristics above can improve the 
      immunogenicities of the weak antigens.
CI  - AJTR Copyright (c) 2022.
FAU - Zhu, Ying
AU  - Zhu Y
AD  - Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical 
      University Hangzhou 310000, Zhejiang, China.
FAU - Huang, Chang-Xin
AU  - Huang CX
AD  - Department of Oncology, The Affiliated Hospital of Hangzhou Normal University 
      Hangzhou 310000, Zhejiang, China.
FAU - Zhang, Le
AU  - Zhang L
AD  - Master Class, Zhejiang Chinese Medical University, The Fourth School of Clinical 
      Medicine Hangzhou 310000, Zhejiang, China.
FAU - Wang, Ze-Fang
AU  - Wang ZF
AD  - Master Class, Hangzhou Normal University, The School of Medicine Hangzhou 
      3100000, Zhejiang, China.
FAU - Zhao, Dong-Li
AU  - Zhao DL
AD  - Master Class, Zhejiang Chinese Medical University, The Fourth School of Clinical 
      Medicine Hangzhou 310000, Zhejiang, China.
FAU - Ding, Fei
AU  - Ding F
AD  - Department of Oncology, The Affiliated Hospital of Hangzhou Normal University 
      Hangzhou 310000, Zhejiang, China.
FAU - Zhang, Si-Yu
AU  - Zhang SY
AD  - Department of Oncology, The Affiliated Hospital of Hangzhou Normal University 
      Hangzhou 310000, Zhejiang, China.
FAU - Li, Yong-Qiang
AU  - Li YQ
AD  - Department of Oncology, The Affiliated Hospital of Hangzhou Normal University 
      Hangzhou 310000, Zhejiang, China.
FAU - Chen, Ling-Zhi
AU  - Chen LZ
AD  - Department of Blood Transfusion, The First Hospital of Jiaxing, Affiliated 
      Hospital of Jiaxing University Jiaxing 314000, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20220715
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC9360904
OTO - NOTNLM
OT  - Residue substitution
OT  - T cell activation
OT  - molecular dynamics simulation
OT  - pi-stacking (pi-stacking)
COIS- None.
EDAT- 2022/08/13 06:00
MHDA- 2022/08/13 06:01
PMCR- 2022/07/15
CRDT- 2022/08/12 02:58
PHST- 2022/04/28 00:00 [received]
PHST- 2022/06/23 00:00 [accepted]
PHST- 2022/08/12 02:58 [entrez]
PHST- 2022/08/13 06:00 [pubmed]
PHST- 2022/08/13 06:01 [medline]
PHST- 2022/07/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2022 Jul 15;14(7):5164-5177. eCollection 2022.