PMID- 34356680
OWN - NLM
STAT- MEDLINE
DCOM- 20211006
LR  - 20211006
IS  - 2218-273X (Electronic)
IS  - 2218-273X (Linking)
VI  - 11
IP  - 7
DP  - 2021 Jul 19
TI  - Can Glycosylation Mask the Detection of MHC Expressing p53 Peptides by T Cell 
      Receptors?
LID - 10.3390/biom11071056 [doi]
LID - 1056
AB  - Proteins of the major histocompatibility complex (MHC) class I, or human 
      leukocyte antigen (HLA) in humans interact with endogenous peptides and present 
      them to T cell receptors (TCR), which in turn tune the immune system to recognize 
      and discriminate between self and foreign (non-self) peptides. Of especial 
      importance are peptides derived from tumor-associated antigens. T cells 
      recognizing these peptides are found in cancer patients, but not in cancer-free 
      individuals. What stimulates this recognition, which is vital for the success of 
      checkpoint based therapy? A peptide derived from the protein p53 (residues 
      161-169 or p161) was reported to show this behavior. T cells recognizing this 
      unmodified peptide could be further stimulated in vitro to create effective 
      cancer killing CTLs (cytotoxic T lymphocytes). We hypothesize that the underlying 
      difference may arise from post-translational glycosylation of p161 in normal 
      individuals, likely masking it against recognition by TCR. Defects in 
      glycosylation in cancer cells may allow the presentation of the native peptide. 
      We investigate the structural consequences of such peptide glycosylation by 
      investigating the associated structural dynamics.
FAU - Nguyen, Thanh Binh
AU  - Nguyen TB
AD  - Division of Biomolecular Structure to Mechanism, Bioinformatics Institute, Agency 
      for Science, Technology and Research (A*STAR), Singapore 138671, Singapore.
FAU - Lane, David P
AU  - Lane DP
AD  - p53 Laboratory, Agency for Science, Technology and Research (A*STAR), Singapore 
      138648, Singapore.
FAU - Verma, Chandra S
AU  - Verma CS
AUID- ORCID: 0000-0003-0733-9798
AD  - Division of Biomolecular Structure to Mechanism, Bioinformatics Institute, Agency 
      for Science, Technology and Research (A*STAR), Singapore 138671, Singapore.
AD  - School of Biological Sciences, College of Science, Nanyang Technological 
      University, Singapore 637551, Singapore.
AD  - Department of Biological Sciences, Faculty of Science, National University of 
      Singapore, Singapore 117543, Singapore.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210719
PL  - Switzerland
TA  - Biomolecules
JT  - Biomolecules
JID - 101596414
RN  - 0 (HLA-A24 Antigen)
RN  - 0 (Human Immunodeficiency Virus Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Antigen, T-Cell)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/metabolism
MH  - Glycosylation
MH  - HLA-A24 Antigen/*chemistry/*metabolism
MH  - Human Immunodeficiency Virus Proteins/chemistry/metabolism
MH  - Humans
MH  - Hydrogen Bonding
MH  - Models, Molecular
MH  - Molecular Dynamics Simulation
MH  - Peptide Fragments/chemistry/metabolism
MH  - Protein Conformation
MH  - Receptors, Antigen, T-Cell/chemistry/*metabolism
MH  - Tumor Suppressor Protein p53/chemistry/*metabolism
PMC - PMC8301869
OTO - NOTNLM
OT  - HLA-A24
OT  - glycosylation
OT  - molecular dynamics
OT  - p53
COIS- CSV is the cofounder of Sinopsee Therapeutics and Aplomex Pte Ltd.; the authors 
      declare no conflict of interests.
EDAT- 2021/08/07 06:00
MHDA- 2021/10/07 06:00
PMCR- 2021/07/19
CRDT- 2021/08/06 12:20
PHST- 2021/05/18 00:00 [received]
PHST- 2021/06/28 00:00 [revised]
PHST- 2021/07/07 00:00 [accepted]
PHST- 2021/08/06 12:20 [entrez]
PHST- 2021/08/07 06:00 [pubmed]
PHST- 2021/10/07 06:00 [medline]
PHST- 2021/07/19 00:00 [pmc-release]
AID - biom11071056 [pii]
AID - biomolecules-11-01056 [pii]
AID - 10.3390/biom11071056 [doi]
PST - epublish
SO  - Biomolecules. 2021 Jul 19;11(7):1056. doi: 10.3390/biom11071056.