Identification of type B-specific and cross-reactive cytotoxic T-lymphocyte responses to Epstein-Barr virus.
Persistent Epstein-Barr virus (EBV) infection is primarily controlled by HLA class I-restricted memory cytotoxic T-cell (CTL) responses which can be reactivated in vitro by stimulation of peripheral blood lymphocytes with autologous lymphoblastoid cell lines. During an investigation of a donor infected by both type A and type B EBV, CTL specific for type B EBV were isolated. The CTL were found to recognize an epitope encoded by the EBNA-6B gene. The minimal epitope sequence was identified as QNGALAINTF, corresponding to residues 213 to 222 in the EBNA-6B protein, and presentation of this epitope was shown to be via HLA B62 (B15). This is the first report of the characterization of an epitope that is EBV type B specific. CTL recognizing sequences common to type A and type B EBV were identified as well. A cross-reactive epitope recognized by these CTL was encoded within the EBNA-6 gene of both type A and type B. This minimal sequence for this epitope was LLDFVRFMGV (residues 284 to 293 in both types), and the epitope was restricted through HLA A*0201. This second epitope sequence overlaps with a published EBV B44-restricted epitope (EENLLDFVRF). The implications of these findings are discussed with respect to the design and efficacy of epitope-based vaccines.
Kerr
B M
BM
Queensland Institute of Medical Research, The Bancroft Centre, Brisbane, Australia. bevK@qimr.edu.au
Kienzle
N
N
Burrows
J M
JM
Cross
S
S
Silins
S L
SL
Buck
M
M
Benson
E M
EM
Coupar
B
B
Moss
D J
DJ
Sculley
T B
TB
D000293:Adolescent; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002478:Cells, Cultured; D003429:Cross Reactions; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007244:Infectious Mononucleosis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D015235:HLA-B Antigens