PMID- 21538979
OWN - NLM
STAT- MEDLINE
DCOM- 20110909
LR  - 20110627
IS  - 1521-4141 (Electronic)
IS  - 0014-2980 (Linking)
VI  - 41
IP  - 7
DP  - 2011 Jul
TI  - Structural insights into the binding of hepatitis B virus core peptide to HLA-A2 
      alleles: towards designing better vaccines.
PG  - 2097-106
LID - 10.1002/eji.201041370 [doi]
AB  - Binding of specific antigenic peptides with human leukocyte antigen (HLA) 
      molecules is a prerequisite for the initiation of T-cell responses and structural 
      information about the peptide-HLA complex is essential for the detailed 
      understanding of such interactions. HLA-A2 is the most prevalent HLA allele 
      globally but aside from A*02:01 there is a significant lack of crystal 
      structures, particularly for alleles that occur in high frequencies among Asian 
      populations. Here, we report three HLA-A2 structures with the immunodominant 
      hepatitis B core antigen 18-27 (HBcAg18-27) epitope, namely A*02:03, A*02:06, and 
      A*02:07 at resolutions of 2.16, 1.70, and 1.75 A respectively. This comparative 
      analysis reveals that minor polymorphic residue changes between different HLA 
      alleles can induce significant alterations in the major histocompatibility 
      complex-peptide interface, and introduce conformational changes in the p3-p8 
      peptide region. Circular dichroism analysis demonstrated the HLA-A2-peptide 
      complexes to have a hierarchy of thermostability and binding affinity in the 
      order of A*02:06>A*02:07>A*02:01>A*02:03. Our findings provide structural 
      insights into the varied HLA-A2 allele binding of the hepatitis B core antigen 
      18-27 epitope and the data suggest that chemical modifications of the peptide 
      side chains could be a promising strategy to modulate and improve HLA-A2-peptide 
      binding affinity for vaccine design.
CI  - Copyright (c) 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
FAU - Liu, Jingxian
AU  - Liu J
AD  - Singapore Immunology Network, A*STAR, Immunos, Singapore.
FAU - Chen, Kenneth Y
AU  - Chen KY
FAU - Ren, Ee C
AU  - Ren EC
LA  - eng
SI  - PDB/3OX8
SI  - PDB/3OXR
SI  - PDB/3OXS
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Eur J Immunol
JT  - European journal of immunology
JID - 1273201
RN  - 0 (HLA-A2 Antigen)
RN  - 0 (Hepatitis B Core Antigens)
RN  - 0 (Hepatitis B Vaccines)
RN  - 0 (Immunodominant Epitopes)
SB  - IM
MH  - Alleles
MH  - Cell Line
MH  - Circular Dichroism
MH  - Crystallography, X-Ray
MH  - HLA-A2 Antigen/*chemistry/genetics/immunology/*metabolism
MH  - Hepatitis B Core Antigens/*chemistry/immunology/*metabolism
MH  - *Hepatitis B Vaccines
MH  - Hepatitis B virus/*immunology
MH  - Humans
MH  - Immunodominant Epitopes
MH  - Protein Binding
MH  - Protein Conformation
EDAT- 2011/05/04 06:00
MHDA- 2011/09/10 06:00
CRDT- 2011/05/04 06:00
PHST- 2011/05/04 06:00 [entrez]
PHST- 2011/05/04 06:00 [pubmed]
PHST- 2011/09/10 06:00 [medline]
AID - 10.1002/eji.201041370 [doi]
PST - ppublish
SO  - Eur J Immunol. 2011 Jul;41(7):2097-106. doi: 10.1002/eji.201041370.