PMID- 7547693
OWN - NLM
STAT- MEDLINE
DCOM- 19951106
LR  - 20190512
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 7
IP  - 4
DP  - 1995 Apr
TI  - HLA-A0201 and HLA-B7 binding peptides in the EBV-encoded EBNA-1, EBNA-2 and 
      BZLF-1 proteins detected in the MHC class I stabilization assay. Low proportion 
      of binding motifs for several HLA class I alleles in EBNA-1.
PG  - 653-63
AB  - B lymphocytes immortalized with EBV in vitro, lymphoblastoid cell lines (LCL), 
      express eight EBV-encoded proteins, EBV nuclear antigens -1 to -6 (EBNA-1 to -6), 
      and latent membrane proteins 1 and 2 (LMP 1 and 2). After appropriate 
      stimulations of blood lymphocytes from seropositive individuals, MHC-restricted 
      cytotoxic T cells (CTL), which lyse LCL cells, can be generated in vitro. Such 
      CTLs can recognize EBNA-2 to -6, and LMP 1 and 2, but not EBNA-1-derived peptides 
      presented on the cell surfaces. We posed the question whether this exceptional 
      feature of EBNA-1 is due to lack of MHC class I binding peptides. A computer 
      search for 11 human leukocyte antigen (HLA) alleles showed that EBNA-1 has a 
      lower number and lower proportion of relevant binding motifs to several alleles 
      than EBNA-2 to -6 and LMP 1 and 2. The low motif numbers in EBNA-1 is in line 
      with its apparent failure to generate a CTL response, and it may be the 
      consequence of immunoselection allowing the existence of EBV genome-carrying B 
      cells in the immunocompetent hosts. The binding capacities of synthetic peptides 
      of EBNA-1 and -2 and of the immediate early lytic cycle protein BZLF-1 to 
      HLA-A0201 (A2) and HLA-B7 molecules were tested in an MHC stabilization assay. 
      The peptide transporter-deficient T2 line, which expresses a low level of HLA-A2 
      and its HLA-B7 transfectant subline, were used for this purpose because 
      specifically bound peptides elevate the surface expression of these MHC 
      molecules. Of five synthetic nonamer EBNA-1 peptides which include the relevant 
      binding motif, four bound to A2. In a series of 20-amino acid-long overlapping 
      EBNA-1 peptides none showed binding to A2, while eight peptides bound to B7. Two 
      20-amino acid-long EBNA-2 and seven BZLF-1 peptides were identified as A2 
      binders, and four EBNA-2 and eight BZLF-1 peptides bound to B7. Thus, we have 
      exclude the possibility that the inability of the EBNA-1 protein to generate 
      HLA-restricted CTLs could be due to the lack of HLA class I binding peptides in 
      its sequence. The finding that several EBNA-1 peptides could bind to these two 
      HLa molecules does not, however, necessarily reflect the natural situation 
      because the peptides may not be processed and/or transported to the cell 
      surfaces. We have stimulated lymphocytes of healthy donors with relevant HLA 
      types with the autologous LCL.(ABSTRACT TRUNCATED AT 400 WORDS)
FAU - Stuber, G
AU  - Stuber G
AD  - Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
FAU - Dillner, J
AU  - Dillner J
FAU - Modrow, S
AU  - Modrow S
FAU - Wolf, H
AU  - Wolf H
FAU - Szekely, L
AU  - Szekely L
FAU - Klein, G
AU  - Klein G
FAU - Klein, E
AU  - Klein E
LA  - eng
GR  - 5 RO1 CA25250/CA/NCI NIH HHS/United States
GR  - CA30264/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Antigens, Viral)
RN  - 0 (BZLF1 protein, Herpesvirus 4, Human)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Epstein-Barr Virus Nuclear Antigens)
RN  - 0 (HLA-A Antigens)
RN  - 0 (HLA-B7 Antigen)
RN  - 0 (Trans-Activators)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - *Alleles
MH  - Amino Acid Sequence
MH  - Antigens, Viral/metabolism
MH  - DNA-Binding Proteins/metabolism
MH  - Epstein-Barr Virus Nuclear Antigens
MH  - HLA-A Antigens/*metabolism
MH  - HLA-B7 Antigen/*metabolism
MH  - Herpesvirus 4, Human/immunology/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Protein Binding/immunology
MH  - Trans-Activators/metabolism
MH  - Viral Proteins/immunology/*metabolism
EDAT- 1995/04/01 00:00
MHDA- 1995/04/01 00:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 1995/04/01 00:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
AID - 10.1093/intimm/7.4.653 [doi]
PST - ppublish
SO  - Int Immunol. 1995 Apr;7(4):653-63. doi: 10.1093/intimm/7.4.653.