title: EBV peptide epitope sensitization restores human cytotoxic T cell recognition of Burkitt's lymphoma cells. Evidence for a critical role for ICAM-2.
abstract: 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.
authors.affiliation: Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Khanna
authors.forename: S R
authors.initials: SR
authors.lastname: Burrows
authors.forename: A
authors.initials: A
authors.lastname: Suhrbier
authors.forename: C A
authors.initials: CA
authors.lastname: Jacob
authors.forename: H
authors.initials: H
authors.lastname: Griffin
authors.forename: I S
authors.initials: IS
authors.lastname: Misko
authors.forename: T B
authors.initials: TB
authors.lastname: Sculley
authors.forename: M
authors.initials: M
authors.lastname: Rowe
authors.forename: A B
authors.initials: AB
authors.lastname: Rickinson
authors.forename: D J
authors.initials: DJ
authors.lastname: Moss
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD; D000956:Antigens, Viral / Q000276:immunology*; D002051:Burkitt Lymphoma / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000502:physiology*; D003601:Cytotoxicity Tests, Immunologic; D004268:DNA-Binding Proteins / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008969:Molecular Sequence Data; D010641:Phenotype; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1