Characterization of T-cell receptor V beta repertoire in ovarian tumour-reacting CD3+ CD8+ CD4- CTL lines.
T cells from tumour infiltrating lymphocytes (TIL) cultured in media containing IL-2 were shown to mediate in vitro and in vivo antitumor responses. To characterize the T-cell antigen receptor (TCR) V beta expression in autologous cytotoxic effectors we isolated CD3+ CD8+ CD4- cells from cultures of TIL and tumour-associated lymphocytes (TAL) and analysed the TCR V beta repertoire of CD3+ CD8+ CD4- lines of known HLA-A, -B and -C phenotype, using polymerase chain reaction (PCR). These lines showed preferential lysis of autologous tumours and lysed, to a much lesser extent, NK and LAK cell-sensitive targets. Tumour lysis was inhibited by antibodies to CD3 and MHC class I antigens indicating that they are cytotoxic T lymphocytes (CTL). These CD8+ CTL lines expressed a broad distribution of TCR V beta repertoire which was dominated by particular groups of V beta families in each CTL line. However, no predominant expression of one or the same V beta segment in all CTL lines was observed although statistical correlations between V beta family usage and magnitude of the antitumour cytolytic response were found. These results suggest that certain TCR V beta families may be selected by antigen in ovarian tumour-reactive T cells and this selection may be affected by Ag expression, and/or host factors. To our knowledge, this is the first documentation of TCR V beta repertoire of human ovarian tumour-reactive CD3+ CD8+ CD4- CTL from different individuals of known HLA types.
Fisk
B
B
Department of Gynecologic Oncology, University of Texas M.D. Anderson Cancer Center, Houston.
Flytzanis
C N
CN
Pollack
M S
MS
Wharton
J T
JT
Ioannides
C G
CG
Flytzanes
C N
CN
D001324:Autoantigens / Q000276:immunology; D015139:Blotting, Southern; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D005434:Flow Cytometry; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000276:immunology*; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D001324:Autoantigens; D006680:HLA Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta