PMID- 31723204
OWN - NLM
STAT- MEDLINE
DCOM- 20201112
LR  - 20230106
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Nov 13
TI  - Crystal structure of suboptimal viral fragments of Epstein Barr Virus Rta 
      peptide-HLA complex that stimulate CD8 T cell response.
PG  - 16660
LID - 10.1038/s41598-019-53201-6 [doi]
LID - 16660
AB  - Peptides presented by Human leukocyte antigen (HLA) class-I molecules are 
      generally 8-10 amino acids in length. However, the predominant pool of peptide 
      fragments generated by proteasomes is less than 8 amino acids in length. Using 
      the Epstein - Barr virus (EBV) Rta-epitope (ATIGTAMYK, residues 134-142) 
      restricted by HLA-A*11:01 which generates a strong immunodominant response, we 
      investigated the minimum length of a viral peptide that can constitute a viral 
      epitope recognition by CD8 T cells. The results showed that Peripheral blood 
      mononuclear cells (PBMCs) from healthy donors can be stimulated by a viral 
      peptide fragment as short as 4-mer (AMYK), together with a 5-mer (ATIGT) to 
      recapitulate the full length EBV Rta epitope. This was confirmed by generating 
      crystals of the tetra-complex (2 peptides, HLA and beta2-microglobulin). The solved 
      crystal structure of HLA-A*11:01 in complex with these two short peptides 
      revealed that they can bind in the same orientation similar to parental peptide 
      (9-mer) and the free ends of two short peptides acquires a bulged conformation 
      that is directed towards the T cell receptor. Our data shows that suboptimal 
      length of 4-mer and 5-mer peptides can complement each other to form a 
      stable peptide-MHC (pMHC) complex.
FAU - Huan, Xuelu
AU  - Huan X
AD  - Singapore Immunology Network, 8A Biomedical Grove, #03-06 Immunos, Singapore, 
      138648, Singapore.
FAU - Zhuo, Ziyi
AU  - Zhuo Z
AD  - Singapore Immunology Network, 8A Biomedical Grove, #03-06 Immunos, Singapore, 
      138648, Singapore.
FAU - Xiao, Ziwei
AU  - Xiao Z
AD  - Singapore Immunology Network, 8A Biomedical Grove, #03-06 Immunos, Singapore, 
      138648, Singapore.
FAU - Ren, Ee Chee
AU  - Ren EC
AD  - Singapore Immunology Network, 8A Biomedical Grove, #03-06 Immunos, Singapore, 
      138648, Singapore. ren_ee_chee@immunol.a-star.edu.sg.
AD  - Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, 
      National University of Singapore, 5 Science Drive 2, Singapore, 119260, 
      Singapore. ren_ee_chee@immunol.a-star.edu.sg.
LA  - eng
PT  - Journal Article
DEP - 20191113
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (BRLF1 protein, Human herpesvirus 4)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (HLA-A Antigens)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Trans-Activators)
SB  - IM
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Epitopes, T-Lymphocyte/chemistry/immunology
MH  - Epstein-Barr Virus Infections/*immunology/virology
MH  - HLA-A Antigens/*chemistry/immunology
MH  - Herpesvirus 4, Human/*immunology
MH  - Humans
MH  - Immediate-Early Proteins/*chemistry/immunology
MH  - Leukocytes, Mononuclear/*immunology/virology
MH  - Peptide Fragments/*chemistry/immunology
MH  - Protein Conformation
MH  - T-Lymphocytes, Cytotoxic/immunology
MH  - Trans-Activators/*chemistry/immunology
PMC - PMC6853878
COIS- The authors declare no competing interests.
EDAT- 2019/11/15 06:00
MHDA- 2020/11/13 06:00
PMCR- 2019/11/13
CRDT- 2019/11/15 06:00
PHST- 2019/06/17 00:00 [received]
PHST- 2019/10/29 00:00 [accepted]
PHST- 2019/11/15 06:00 [entrez]
PHST- 2019/11/15 06:00 [pubmed]
PHST- 2020/11/13 06:00 [medline]
PHST- 2019/11/13 00:00 [pmc-release]
AID - 10.1038/s41598-019-53201-6 [pii]
AID - 53201 [pii]
AID - 10.1038/s41598-019-53201-6 [doi]
PST - epublish
SO  - Sci Rep. 2019 Nov 13;9(1):16660. doi: 10.1038/s41598-019-53201-6.