scholarly journals The life span of major histocompatibility complex-peptide complexes influences the efficiency of presentation and immunogenicity of two class I-restricted cytotoxic T lymphocyte epitopes in the Epstein-Barr virus nuclear antigen 4.

1996 ◽  
Vol 183 (3) ◽  
pp. 915-926 ◽  
Author(s):  
V Levitsky ◽  
Q J Zhang ◽  
J Levitskaya ◽  
M G Masucci
Keyword(s):  
Cell Surface ◽  
T Lymphocyte ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Nuclear Antigen ◽  
Ctl Epitopes ◽  
Barr Virus ◽  
Wide Range ◽  
Epstein Barr

We have investigated the reactivity to two human histocompatibility leukocyte antigen (HLA) A11-restricted cytotoxic T lymphocyte (CTL) epitopes derived from amino acids 416-424 (IVTDFSVIK, designated IVT) and 399-408 (AVFDRKSVAK, designated AVF) of the Epstein-Barr virus (EBV) nuclear antigen (EBNA) 4. A strong predominance of CTL clones specific for the IVT epitope was demonstrated in polyclonal cultures generated by stimulation of lymphocytes from the EBV-seropositive donor BK with the autologous B95.8 virus-transformed lymphoblastoid cell line (LCL). This was not due to intrinsic differences of CTL efficiency since clones specific for the two epitopes lysed equally well A11-positive phytohemagglutinin blasts and LCLs pulsed with the relevant synthetic peptide. Irrespective of the endogenous levels of EBNA4 expression, untreated LCLs were lysed more efficiently by the IVT-specific effectors, suggesting that a higher density of A11-IVT complexes is presented at the cell surface. In accordance, 10-50-fold higher amounts of IVT peptides were found in high-performance liquid chromatography fractions of acid extracts corresponding to an abundance of about 350-12,800 IVT and 8-760 AVF molecules per cell. Peptide-mediated competition of CTL sensitization, transport assays in streptolysin-O permeabilized cells, and induction of A11 expression in the transporter associated with antigen presentation-deficient T2/A11 transfectant demonstrated that the IVT and AVF peptides bind with similar affinities to A11, are translocated with equal efficiency to the endoplasmic reticulum, and form complexes of comparable stability over a wide range of temperature and pH conditions. A rapid surface turnover of A11 molecules containing the AVF peptide was demonstrated in metabolically active T2/A11 cells corresponding to a half-life of approximately 3.5 as compared to approximately 2 h for molecules induced at 26 degrees C in the absence of exogenous peptides and >12 h for IVT-containing complexes. This difference in persistence is likely to determine the representation of individual class I-restricted CTL epitopes within the cell surface pool of molecules, and may be an important factor contributing to their immunogenicity.

scholarly journals Characterization of an human leucocyte antigen A2-restricted Epstein-Barr virus nuclear antigen-1-derived cytotoxic T-lymphocyte epitope

Immunology ◽  
2010 ◽  
Vol 129 (3) ◽  
pp. 386-395 ◽  
Author(s):  
Diego Marescotti ◽  
Federica Destro ◽  
Anna Baldisserotto ◽  
Mauro Marastoni ◽  
Giuseppe Coppotelli ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Epstein Barr Virus ◽  
Human Leucocyte Antigen ◽  
Cytotoxic T Lymphocyte ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals T cell responses and virus evolution: loss of HLA A11-restricted CTL epitopes in Epstein-Barr virus isolates from highly A11-positive populations by selective mutation of anchor residues.

1994 ◽  
Vol 179 (4) ◽  
pp. 1297-1305 ◽  
Author(s):  
P O de Campos-Lima ◽  
V Levitsky ◽  
J Brooks ◽  
S P Lee ◽  
L F Hu ◽  
...  
Keyword(s):  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Virus Evolution ◽  
Nuclear Antigen ◽  
Ctl Epitopes ◽  
Barr Virus ◽  
Southern Chinese ◽  
Epstein Barr ◽  
Ctl Responses

Epstein-Barr virus (EBV) is a B lymphotropic herpesvirus of humans that elicits strong HLA class I-restricted cytotoxic T lymphocyte (CTL) responses. An influence of such responses on virus evolution was first suggested by our finding that EBV isolates from the highly HLA A11-positive Papua New Guinea (PNG) population carried a lys-thr mutation at residue 424 of the nuclear antigen EBV-encoded nuclear antigen (EBNA4) that destroyed the immunodominant target epitope for A11-restricted CTL recognition. Here we turn to a much larger population, Southern Chinese, where the A11 allele is again present in over 50% of the individuals. Each of 23 EBV isolates analyzed from this population were also mutated in the EBNA4 416-424 epitope, the mutations selectively involving one of the two anchor residues in positions 2 (417 val-leu) or 9 (424 lys-asp, -arg or -thr) that are critical for A11-peptide interaction. The majority of the Chinese isolates and all 10 PNG isolates also carried mutations affecting positions 1 and 2 of the next most immunodominant A11-restricted epitope, EBNA4 residues 399-408. These changes clearly affected antigenicity since A11-positive lymphoblastoid cell lines (LCLs) carrying these mutant EBV strains were not recognized by A11-restricted CTLs raised against the prototype B95.8 virus. Furthermore, Chinese donors naturally infected with these mutant viruses did not mount detectable A11-restricted CTL responses on in vitro stimulation with autologous LCL cells carrying either the B95.8 or their endogenous EBV strain. In two different highly A11-positive populations, therefore, immune pressure appears to have selected for resident EBV strains lacking immunodominant A11-restricted CTL epitopes.

scholarly journals The B Subunit of Escherichia coli Heat-Labile Enterotoxin Enhances CD8+ Cytotoxic-T-Lymphocyte Killing of Epstein-Barr Virus-Infected Cell Lines

2003 ◽  
Vol 77 (7) ◽  
pp. 4298-4305 ◽  
Author(s):  
Kong-Wee Ong ◽  
A. Douglas Wilson ◽  
Timothy R. Hirst ◽  
Andrew J. Morgan
Keyword(s):  
Cell Lines ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Class I ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
B Subunit ◽  
Histocompatibility Complex ◽  
Epstein Barr

ABSTRACT Epstein-Barr virus (EBV) is associated with a number of important human cancers, including nasopharyngeal carcinoma, gastric carcinoma, and Hodgkin's lymphoma. These tumors express a viral nuclear antigen, EBV nuclear antigen 1 (EBNA1), which cannot be presented to T cells in a major histocompatibility complex class I context, and the viral latent membrane proteins (LMPs). Although the LMPs are expressed in these tumors, no effective immune response is made. We report here that exposure to the cholera-like enterotoxin B subunit (EtxB) in EBV-infected lymphoblastoid cell lines (LCLs) enhances their susceptibility to killing by LMP-specific CD8+ cytotoxic T lymphocytes (CTLs) in a HLA class I-restricted manner. CTL killing of LCLs is dramatically increased through both transporter-associated protein-dependent and -independent epitopes after EtxB treatment. The use of mutant B subunits revealed that the enhanced susceptibility of LCLs to CTL killing is dependent on the B subunit's interaction with GM1 but not its signaling properties. These important findings could underpin the development of novel approaches to treating EBV-associated malignancies and may offer a general approach to increasing the presentation of other tumor and viral antigens.

scholarly journals Multiple HLA A11-restricted cytotoxic T-lymphocyte epitopes of different immunogenicities in the Epstein-Barr virus-encoded nuclear antigen 4.

1993 ◽  
Vol 67 (3) ◽  
pp. 1572-1578 ◽  
Author(s):  
R Gavioli ◽  
M G Kurilla ◽  
P O de Campos-Lima ◽  
L E Wallace ◽  
R Dolcetti ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Epstein Barr Virus ◽  
Cytotoxic T Lymphocyte ◽  
Nuclear Antigen ◽  
Barr Virus ◽  
Epstein Barr
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