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S R Burrows

Publications and source records attributed to S R Burrows.

At least 55 records · Page 3Linked to original sources
PubMed1996

Peptide transporter (TAP-1 and TAP-2)-independent endogenous processing of Epstein-Barr virus (EBV) latent membrane protein 2A: implications for cytotoxic T-lymphocyte control of EBV-associated malignancies.

Major histocompatibility [correction of histocampatability] complex (MHC) class I-restricted cytotoxic T lymphocytes (CTLs) recognizing Epstein-Barr virus (EBV) latent antigens play a pivotal role in restricting the proliferation of EBV-infected normal B cells. However, it is now well established that most of the EBV-associated malignancies escape this potent CTL response in vivo. This resistance to immune surveillance is not due to an obvious CTL dysfunction but has been partly attributed to the down-regulation of the peptide transporters, TAP-1 and TAP-2, thus restricting the endogenous loading of MHC class I molecules with peptides derived from viral nuclear antigens. In the present study we have explored the possibility that EBV latent membrane protein 2A (LMP2A), which is often expressed in many of the EBV-associated malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors, can be endogenously processed through an alternative, TAP-1- and TAP-2-independent pathway. The data presented in this study clearly demonstrate not only that LMP2A can be processed by a TAP-independent mechanism but also that tumor cells with down-regulated TAP expression can be efficiently recognized by LMP2A-specific T cells following infection with recombinant vaccinia virus encoding this protein. We propose that since LMP2A is a membrane protein, it is directly translocated into the secretory pathway and the processing enzymes present in the endoplasmic reticulum are capable of generating the relevant peptide epitopes for MHC binding. The present finding of TAP-1- and TAP-2-independent presentation of LMP2A epitopes suggests a novel mechanism for immune targeting of EBV-positive malignancies, such as nasopharyngeal carcinoma and Hodgkin's disease tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Expression of p53, bcl-2, bax, bcl-x2 and c-myc in radiation-induced apoptosis in Burkitt's lymphoma cells.

Apoptosis, a form of physiological cell death, is a genetically determined program essential for normal development and maintenance of tissues, which has been linked to a variety of gene products. We have examined the susceptibility to radiation-induced apoptosis of cell lines derived from the human B cell tumour, Burkitt's lymphoma (BL), displaying a variety of phenotypic characteristics and expressing genes implicated in apoptosis at different levels. The susceptibility to apoptosis following gamma radiation varied significantly amongst the lines. Cell lines with wild type p53 were susceptible to radiation-induced apoptosis but two of five BL lines with only mutant p53 allele also displayed similar susceptibility. Some BL cell lines that expressed bcl-2 at levels comparable with Epstein-Barr virus (EBV) transformed normal B cells were highly susceptible to gamma radiation-induced apoptosis, whereas others expressing low levels were resistant. When these lines were analysed for bax and bcl-X(L) expression again no correlation was observed with susceptibility or resistance to apoptosis. Two BL cell lines having deregulated expression of c-myc were resistant to the induction of apoptosis while two others which had regulated c-myc expression were susceptible. Thus the status of p53, c-myc, bcl-2, bcl-X(L) and bax is not sufficiently informative in BL lines to predict susceptibility to radiation-induced apoptosis.

Journal Article↗
PubMed1995

Isolation of cytotoxic T lymphocytes from healthy seropositive individuals specific for peptide epitopes from Epstein-Barr virus nuclear antigen 1: implications for viral persistence and tumor surveillance.

The question of whether Epstein-Barr nuclear antigen 1 (EBNA1) includes cytotoxic T lymphocyte (CTL) epitopes has generated considerable scientific interest, primarily due to its important implications for the overall biology of Epstein-Barr virus (EBV). Earlier studies have suggested that EBV-associated malignancies that express only EBNA1 escape virus-specific immune surveillance since this antigen is not a target for CTL recognition. In the present report we have used a modified protocol to demonstrate that EBNA1 includes sequences which can be recognized by both polyclonal and clonal CTLs. CD4+ CTL clones were isolated from a healthy, seropositive donor that recognized the peptide epitope TSLYNLRRGTALA from EBNA1 in association with HLA DR1. Interestingly, these CTLs are unable to lyse EBV-infected B cells suggesting that EBNA1 may not be endogenously processed and/or presented to the host CTL response. Despite recent suggestions that glycine-alanine repeat sequences within EBNA1 can inhibit endogenous processing, target cells infected with recombinant vaccinia vectors encoding truncated EBNA1 proteins, without these repeat sequences, were not recognized by this CTL clone. Thus it seems that the presence of glycine-alanine repeats is not responsible for inhibiting the processing of the class II-restricted epitope defined in this study. These results substantiate the view that EBV-infected normal and malignant cells, where viral gene expression is limited to EBNA1, can resist CTL-mediated immune surveillance in vivo.

Amino Acid Sequence↗
PubMed1995

T cell receptor repertoire for a viral epitope in humans is diversified by tolerance to a background major histocompatibility complex antigen.

Two unusual characteristics of the memory response to the immunodominant Epstein-Barr virus (EBV) epitope FLRGRAYGL, which associates with HLA B8, have provided an unique opportunity to investigate self tolerance and T cell receptor (TCR) plasticity in humans. First, the response is exceptionally restricted, dominated by cytotoxic T lymphocytes (CTL) with identical TCR protein sequences (Argaet, V. P., C. W. Schmidt, S. R. Burrows, S. L. Silins, M. G. Kurilla, D. L. Doolan, A. Suhrbier, D. J. Moss, E. Kieff, T. B. Sculley, and I. S. Misko. 1994. J. Exp. Med. 180:2335-2340). Second, CTL expressing this receptor are cross-reactive with the alloantigen HLA B* 4402 on uninfected cells (Burrows, S. R., R. Khanna, J. M. Burrows, and D. J. Moss. 1994. J. Exp. Med. 179:1155-1161). No CTL using this conserved public TCR could be reactivated from the peripheral blood of EBV exposed individuals expressing both HLA B8 and B*4402, demonstrating the clonal inactivation of potentially self-reactive T cells in humans. A significant FLRGRAYGL-specific response was still apparent, however, and TCR sequence analysis of multiple CTL clones revealed an oligoclonal TCR repertoire for this determinant within these individuals, using diverse V and J gene segments and CDR3 regions. In addition, a significant public TCR component was identified in which several distinct alpha/beta rearrangements are shared by CTL clones from a number of unrelated HLA B8+, B*4402+ donors. The striking dominance of public TCR in the response to this EBV epitope suggests a strong genetic bias in TCR gene recombination. Fine specificity analysis using peptide analogues showed that, of six different antigen receptors for FLRGRAYGL/HLA B8, none associate closely with the peptide's full array of potential TCR contact residues. Whereas the HLA B*4402-cross-reactive receptor binds amino acids toward the COOH terminus of the peptide, others preferentially favor an NH2-terminal determinant, presumably evading an area that mimics a structure presented on HLA B*4402. Thus, tolerance to a background major histocompatibility antigen can effectively diversify the TCR repertoire for a foreign epitope by deflecting the response away from an immunodominant combination of TCR-binding residues.

Amino Acid Sequence↗
PubMed1995

Minimal epitopes expressed in a recombinant polyepitope protein are processed and presented to CD8+ cytotoxic T cells: implications for vaccine design.

The epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL) are generated from cytosolic proteins by proteolytic processing. The nature of the influences exerted by the sequences flanking CTL epitopes on these processing events remains controversial. Here we show that each epitope within an artificial polyepitope protein containing nine minimal CD8+ CTL epitopes in sequence was processed and presented to appropriate CTL clones. Natural flanking sequences were thus not required to direct class I proteolytic processing. In addition, unnatural flanking sequences containing other CTL epitopes did not interfere with processing. The ability of every CTL epitope to be effectively processed from a protein containing only CTL epitopes is likely to find application in the construction of recombinant polyepitope CTL vaccines.

Amino Acid Sequence↗
PubMed1995

Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression.

Group I Burkitt lymphoma (BL) lines retaining the original BL tumor cell phenotype are unable to present endogenously expressed antigens to HLA class I-restricted cytotoxic T cells (CTL) but can be recognized if the relevant HLA class I/peptide epitope complex is reconstituted at the cell surface by exogenous addition of synthetic target peptide. Endogenous antigen-processing function is restored in BL lines that have undergone Epstein-Barr virus (EBV)-induced drift in culture to the group III phenotype typically displayed by EBV-transformed lymphoblastoid cell lines (LCL) of normal B cell origin. We compared group I versus group III cells for their expression of proteasome components, transporter proteins and HLA-class I antigens, all of which are thought to be involved in the endogenous antigen processing pathway. By Western blot analysis, there were not consistent differences in the low molecular mass protein subunits of proteasomes (lmp)-2, lmp-7 and delta, although the mb-1 proteasome subunit was regularly present at higher levels in group I BL lines relative to group III lines or LCL. By contrast there were marked differences in the expression of peptide transporter-associated proteins (Tap), with down-regulation of Tap-1 and Tap-2 in 8/8 and 7/8 group I BL lines, respectively. Surface levels of HLA class I antigens were also consistently lower in group I cells; this was not associated with an intracellular accumulation of free HLA heavy chains, such as is seen in the Tap-deficient T2 processing-mutant line, but instead reflected a reduced rate of HLA class I synthesis in group I cells. Analysis of EBV gene transfectants of the B lymphoma lines BJAB and BL41 showed that the virus-encoded latent membrane protein-1 (LMP1), which is one of several EBV antigens expressed in group III but not in group I cells, was uniquely able to up-regulate expression both of the Tap proteins and HLA class I. Furthermore, this was accompanied by a restoration of antigen-processing function as measured by the ability of these cells to present an endogenously expressed viral antigen to CTL. These effects of LMP1 were similar to those induced in the same cell lines by interferon-gamma treatment. The results implicate both Tap and HLA class I expression as factors limiting the antigen-processing function of BL cells, and suggest that the accessibility of other EBV-associated malignancies to CTL surveillance may be critically dependent upon their LMP1 status.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Immune regulation in Epstein-Barr virus-associated diseases.

Epstein-Barr virus (EBV) is a member of the human herpesvirus family and, like many other herpesviruses, maintains a lifelong latent association with B lymphocytes and a permissive association with stratified epithelium in the oropharynx. Clinical manifestations of primary EBV infection range from acute infectious mononucleosis to an asymptomatic persistent infection. EBV is also associated with a number of malignancies in humans. This review discusses features of the biology of the virus, both in cell culture systems and in the natural host, before turning to the role of the immune system in controlling EBV infection in healthy individuals and in individuals with EBV-associated diseases. Cytotoxic T cells that recognize virally determined epitopes on infected cells make up the major effector arm and control the persistent infection. In contrast, the options for immune control of EBV-associated malignancies are more restricted. Not only is antigen expression restricted to a single nuclear antigen, EBNA1, but also these tumor cells are unable to process EBV latent antigens, presumably because of a transcriptional defect in antigen-processing genes (such as TAP1 and TAP2). The likelihood of producing a vaccine capable of controlling the acute viral infection and EBV-associated malignancies is also discussed.

Antibody Formation↗
PubMed1994

Dominant selection of an invariant T cell antigen receptor in response to persistent infection by Epstein-Barr virus.

To examine T cell receptor (TCR) diversity involved in the memory response to a persistent human pathogen, we determined nucleotide sequences encoding TCR-alpha and -beta chains from HLA-B8-restricted, CD8+ cytotoxic T cell clones specific for an immunodominant epitope (FLRGRAYGL) in Epstein-Barr virus (EBV) nuclear antigen 3. Herein, we show that identical TCR protein sequences are used by clones from each of four healthy unrelated virus carriers; a clone from a fifth varied conservatively at only two residues. This dominant selection of alpha and beta chain rearrangements suggest that a persistent viral infection can select for a highly focused memory response and indicates a strong bias in gene segment usage and recombination. A novel double-step semiquantitative polymerase chain reaction (PCR) procedure and direct sequencing of amplified TCR cDNA from fresh lymphocytes derived from three HLA-B8 individuals detected transcripts specific for the conserved beta chain in an EBV-seropositive donor but not in two seronegative donors. This report describes an unprecedented degree of conservation in TCR selected in response to a natural persistent infection.

Amino Acid Sequence↗
PubMed1994

Epstein-Barr virus-specific cytotoxic T cell response in cardiac transplant recipients.

PBLs from 10 normal seropositive donors, 15 precardiac transplant patients, and 17 postcardiac transplant patients have been assayed for their ability to mount a cytotoxic T cell response to both A- and B-type EBV. Compared with the results obtained with healthy seropositive donors, pre- and posttransplant patients had significantly weaker T cell responses against both A-type and B-type EBV. Analysis of individual patients showed a preferential T cell response to B-type EBV in 4/15 pre- and 6/17 posttransplant patients and a preferential T cell response to A-type EBV in 1/15 pretransplant and 2/17 posttransplant recipients. PBMCs were obtained from patients and analyzed for the presence of A- and B-type EBV using polymerase chain reaction. EBV types detected in the PBMCs of each individual were correlated with their EBV-specific CTL response. The results obtained indicated that the EBV-specific cytotoxic T cell response of these patients matched the EBV types with which they were infected.

Adult↗
PubMed1994

An alloresponse in humans is dominated by cytotoxic T lymphocytes (CTL) cross-reactive with a single Epstein-Barr virus CTL epitope: implications for graft-versus-host disease.

The phenomenon of T cell allorecognition is difficult to accommodate within the framework of a T cell repertoire positively selected in the thymus, unless allorecognition results from the cross-reactions of self-major histocompatibility complex restricted T cells. Herein, we demonstrate the dual specificity of cytotoxic T lymphocyte (CTL) clones for the immunodominant Epstein-Barr virus (EBV) epitope FLRGRAYGL, presented on HLA-B8, and the alloantigen HLA-B*4402. CTL which recognized peptide FLRGRAYGL in association with HLA-B8 could be reactivated in vitro from healthy individuals who had been exposed previously to EBV, using stimulator cells expressing the cross-reacting alloantigen HLA-B*4402. Limiting dilution analysis of the alloresponse to HLA-B*4402 in eight healthy individuals revealed that HLA-B8+, EBV-sero+ donors had higher CTL precursor frequencies for alloantigen HLA-B*4402 than EBV-sero- control donors. It is surprising that the majority (65-100%) of anti-HLA-B*4402 CTL, generated in limiting dilution mixed lymphocyte reactions between responder cells from HLA-B8+, EBV-sero+ individuals and HLA-B*4402+ stimulators, also recognized the EBV CTL epitope FLRGRAYGL/HLA-B8. In contrast to previous studies showing extensive diversity in the T cell repertoire against individual alloantigens, these data demonstrate that the response to an alloantigen can be dominated by CTL cross-reactive with a single viral epitope, thus illustrating a possible mechanism for the frequent clinical association between herpesvirus exposure and graft-versus-host disease after bone marrow transplants.

Amino Acid Sequence↗
PubMed1994

Potential antigenic targets on Epstein-Barr virus-associated tumours and the host response.

There is considerable variation in the degree of expression of viral genes among different tumours associated with Epstein-Barr virus (EBV). Immune control of tumours in immunosuppressed patients (immunoblastic lymphomas) can be exercised through a range of epitopes from cytotoxic T lymphocytes (CTL) covering the full spectrum of latent EBV gene products. A subunit vaccine based on an EBV CTL epitope from one of the latent genes is about to undergo human trial. The options for immune control of Burkitt's lymphoma are more restricted. Antigen expression is limited to a single nuclear antigen, EBNA1, and Burkitt's lymphoma cells are unable to process EBV latent antigens, presumably because of a transcriptional defect in TAP1 and TAP2 genes. In contrast with earlier suggestions that EBNA1 is not a target for CTL, there is a class II-restricted epitope within EBNA1. EBV-infected B cells are unable to process this epitope endogenously. The most promising strategy for developing a vaccine against these tumours is to use a single subunit vaccine that incorporates multiple CTL epitopes from several human pathogens.

Amino Acid Sequence↗
PubMed1994

Endoplasmic reticulum signal sequence facilitated transport of peptide epitopes restores immunogenicity of an antigen processing defective tumour cell line.

The identification of MHC-restricted and tumour-specific cytotoxic T lymphocytes (CTLs) provides strong evidence in support of T cell-mediated immune surveillance against human tumour cells. These CTLs recognize short peptides derived from tumour-associated antigens in conjunction with class I molecules expressed on tumour cells. In contrast to these observations there are now numerous examples to suggest that a number of tumours escape this CTL-mediated control either by down-regulating accessory molecules or by blocking the intracellular processing of tumour-specific antigens. Recently a number of tumour cell lines have been identified which display a transcriptional deficiency of transporters associated with antigen processing (also referred to as TAP). The Epstein-Barr virus (EBV)-associated tumour, Burkitt's lymphoma (BL), is a classic example in this category. In the present study we have restored class I-restricted antigen processing in a BL cell line by transfecting a minigene expression vector encoding a CTL epitope derived from EBV linked to an endoplasmic reticulum translocation signal sequence. These minigene transfected BL cells were not only susceptible to lysis by virus-specific CTL but were also capable of efficiently activating an antigen-specific CTL response. Interestingly, the immunogenicity of these BL cells was not affected by the significantly down-regulated expression of adhesion molecules such as LFA1 alpha, LFA1 beta and LFA3. These findings suggest that resistance of tumour cells to CTL-mediated immune control can be reversed if the relevant peptide epitopes are appropriately presented on the cell surface.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Presentation of endogenous viral peptide epitopes by anti-CD40 stimulated human B cells following recombinant vaccinia infection.

Cytotoxic T lymphocytes (CTLs) recognising viral antigens are an important host defence mechanism in restricting the proliferation of virus-infected cells. Previously, lymphoblastoid cell lines (LCLs) infected with vaccinia recombinants encoding viral proteins have been used to identify specific CTL epitopes. However, to localise the EBV CTL epitopes encoded by Epstein-Barr virus (EBV) transformants, LCLs are an inappropriate host for vaccinia recombinants. In the present study, an alternative host cell for vaccinia infection is described. Initial studies demonstrated that anti-CD40 stimulated human B cells replicated vaccinia virus and expressed EBV nuclear antigen(s) (EBNA) following infection with recombinant vaccinia encoding the appropriate region of the EBV genome. Recombinant vaccinia-infected anti-CD40 stimulated B cell lines were then used to localise target epitopes for a panel of EBV-specific CTL clones. Most importantly, in vitro stimulation of unfractionated mononuclear cells with recombinant vaccinia-infected anti-CD40 B cells activated a memory CTL response. Based on the vaccinia results, screening of peptides from EBNA6 defined the epitope for the EBNA6-specific CTL clones to the sequence KEHVIQNAFRK. This work clearly demonstrates that anti-CD40 stimulated B cell lines not only provide an efficient tool for localising CTL epitopes but also presents an alternative mechanism of reactivating a memory T cell response to any gene product expressed by recombinant vaccinia.

Amino Acid Sequence↗
PubMed1993

EBV peptide epitope sensitization restores human cytotoxic T cell recognition of Burkitt's lymphoma cells. Evidence for a critical role for ICAM-2.

The pathogenesis of EBV+ Burkitt's lymphoma (BL) suggests evasion of the CTL response against EBV. Two important features of this tumor have been previously suggested to explain this immune evasion, (a) absence/low expression of cellular adhesion molecules and (b) restricted expression of EBV latent Ag. To determine the relative importance of these features in relation to evasion of EBV-specific CTL, a group of BL cell lines with variable expression of the aforementioned phenotypic characteristics were assayed for specific CTL lysis after exogenous addition of EBV peptide epitopes. In spite of down-regulated expression of the adhesion molecules LFA-1, LFA-3, and/or ICAM-1, peptide-sensitized BL cells were recognized and lysed by EBV-specific CTL. Moreover, there was no significant difference between the CTL lysis of the BL cells and that of adhesion molecule-positive control cells over a wide range of peptide epitope concentrations. Blocking experiments with mAb to individual adhesion molecules suggested that virus-specific CTL recognition of lymphoblastoid cell lines was dependent on an intact LFA-3/CD2 pathway. In contrast, the CTL recognition of peptide-sensitized BL cells was critically dependent on the LFA-1/ICAM pathway, with an insignificant contribution by CD2/LFA-3. The consistently high expression of ICAM-2 on all BL cell lines suggests that the accessory function in CTL recognition of these cells is mediated by the LFA-1/ICAM-2 pathway. Thus, down-regulation of LFA-1, LFA-3, and/or ICAM-1 expression on BL cells does not provide an absolute barrier to tumor cell recognition by virus-specific CTL. The ability of virus-specific CTL to recognize peptide epitope-sensitized BL cells as efficiently as normal cells has demonstrated the importance of latent Ag expression in the CTL control of EBV+ tumors.

Amino Acid Sequence↗
PubMed1993

Peptide epitope induced apoptosis of human cytotoxic T lymphocytes. Implications for peripheral T cell deletion and peptide vaccination.

Cloned CTL can be induced to undergo apoptosis with cognate peptide epitopes. This phenomenon has been attributed to self recognition and self destruction of individual, isolated CTL and/or Ag-induced cell death. It has been claimed that these mechanism are responsible for extrathymic elimination of primed CTL. In our study the contribution of all known effector mechanisms (single cell self killing, CTL-CTL killing, backward killing, bystander killing, Ag-induced cell death, and veto) to peptide epitope-induced destruction of CTL was evaluated. CTL-CTL killing was found to be the dominant mechanism, with a significant contribution from bystander killing. CTL were as susceptible to peptide-mediated lysis as conventional target cells. CTL, which were actively killing target cells, were not refractory to the lytic mechanisms of other CTL but paradoxically, avoid destruction by their own lytic mediators when delivering the lethal hit. These data imply that mature primed CTL are not deleted in the periphery as a direct result of the lysis of target cells, although, under certain circumstances peripheral CTL-CTL killing may be envisaged when cognate peptide is used for vaccination.

Amino Acid Sequence↗
PubMed1993

Bystander apoptosis induced by CD8+ cytotoxic T cell (CTL) clones: implications for CTL lytic mechanisms.

Cytotoxic T lymphocyte (CTL) mediated killing has classically been associated with a high level of specificity for the target cell. However, when CTL clones and specific target cells were copelleted with innocent bystander cells for which the CTL was not specific, these bystander cells were also lysed. Bystander lysis did not depend on HLA compatibility between effector and bystander cell. Indeed bystander lysis was particularly efficient during cognate synthetic peptide induced CTL-CTL killing. Bystander lysis was species unrestricted. Lytic activity could not be transferred in supernatants nor could it be inhibited by anti-tumor necrosis factor antibodies. Perforin sensitive red blood cells were very inefficiently bystander lysed. Bystander cell death was characterized by DNA fragmentation indicative of apoptosis or programmed cell death. Bystander lysis thus appeared to be due to the apoptotic CTL lytic mediator(s). Importantly, CTL were not resistant to bystander lysis induced by other CTL; nor did they become resistant when they were actively killing target cells. Since it is well established that CTL survive the delivery of their own lytic mediators, these results suggest that CTL induced apoptosis is a membrane mediated event.

Amino Acid Sequence↗
PubMed1992

Localization of Epstein-Barr virus cytotoxic T cell epitopes using recombinant vaccinia: implications for vaccine development.

There is considerable interest in designing an effective vaccine to the ubiquitous Epstein-Barr virus (EBV). An important role for EBV-specific cytotoxic T lymphocytes (CTLs) in eliminating virus-infected cells is well established. Limited studies using a small number of immune donors have defined target epitopes within the latent antigens of EBV. The present study provides an extensive analysis of the distribution of class I-restricted CTL epitopes within EBV-encoded proteins. Using recombinant vaccinia encoding individual EBV latent antigens (Epstein-Barr nuclear antigen [EBNA] 1, 2, 3A, 3B, 3C, LP, and LMP 1), we have successfully localized target epitopes recognized by CTL clones from a panel of 14 EBV-immune donors. Of the 20 CTL epitopes localized, five were defined at the peptide level. Although CTL clones specific for nine epitopes recognized both type 1 and type 2 transformants, a significant number of epitopes (7/16 epitopes for which EBV type specificity was determined) were detected only on type 1 EBV transformants. Vaccinia recombinants encoding EBNA 3A and EBNA 3C were recognized more frequently than any other vaccinia recombinants used in this study, while no CTL epitopes were localized in EBNA 1. Surprisingly, epitope specificity for a large number of EBV-specific CTL clones could not be localized, although vaccinia recombinants used in this study encoded most of the latent antigens of EBV. These results suggest that any EBV vaccine based on CTL epitopes designed to provide widespread protection will need to include not only latent antigen sequences but also other regions of the genome. The apparent inability of human CTLs to recognize EBNA 1 as a target antigen, often the only latent antigen expressed in Burkitt's lymphoma and nasopharyngeal carcinoma, suggests that EBV-specific CTL control of these tumors will not be feasible unless the down-regulation of latent antigens can be reversed.

Amino Acid Sequence↗