Abstract
Tumor-specific expression of Qa-2k antigen coded by the Q5k gene on various mouse tumor cells and immunological response of the host mice to the antigen have been demonstrated [Seo et al. (1992) J Exp Med 175: 547; Tanino et al. (1992) Cancer Immunol Immunother 35: 230]. The possibility was examined that Qa-2 antigen is one of the recognition target molecules of immunopotentiator-induced, H-2-nonrestricted tumoricidal lymphocytes of Qa-2− mice. Lymphocytes stimulated in vivo withP. acnes or culture-induced anomalous killers of B6.K1 mice did not exhibit significant in vitro cytotoxicity against B6.K1 lymphoblasts but lysed their Qa-2,3-congenic counterpart B6 lymphoblasts. To demonstrate the Qa-2 specificity of such cytotoxic cells more precisely, an L cell transformant clone (LQ7b/Kb), which expressed the α1 and α2 domains of the Qa-2 antigen (Q7b gene product), was generated by transfecting a cloned plasmid DNA containing a hybrid gene constructed from the 5′ half of the Q7b gene and the 3′ half of the H-2Kb gene (pQ7b/Kb). Using LQ7b/Kb cells as the target cells and the nylon-wool-nonadherent fraction of lymphocytes fromP. acnes-stimulated (C3H/He × B6.K1)F1 mice (H-2k, Qa-2−) as the effector cells of the in vitro cytotoxicity reaction, the presence of cytotoxic cells that recognize the α1/α2 region of the Q7b gene product was demonstrated. The cytotoxic activity was dependent on T cells bearing T cell receptors of the γ/δ type (TCRγ/δ). The (C3H/He × B6.K1)F1 effector cells, as well as the B6.K1 effector cells also lysed BW5147 lymphoma cells (Qa-2k+) derived from AKR mice (Qa-2−, H-2k). By target-competition experiments it was shown that some of the effector cells lytic to BW5147 were identical to those that lysed LQ7b/Kb. Therefore some of the tumoricidal cells induced by the immunopotentiator interact with the target tumor cells through recognition of the α1/α2 region of the Qa-2k tumor antigen by TCRγ/δ.
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References
Bluestone JA, Cron RQ, Cotterman M, Houlden BA, Matis LA (1988) Structure and specificity of T cell receptor γ/δ on major histocompatibility complex antigen-specific CD3+, CD4−, CD8− lymphocytes. J Exp Med 168: 1899
Bonneville M, Ito K, Krecko EG, Itohara S, Kappes D, Ishida I, Kanagawa O, Janeway CA, Murphy DB, Tonegawa S (1989) Recognition of a self major histocompatibility complex TL region product by γδ T cell-receptors. Proc Natl Acad Sci USA 86: 5928
Born WK, O'Brien RL, Modlin RL (1991) Antigen specificity of γ/δ lymphocytes. FASEB 5: 2699
Ciccone E, Viale O, Bottino C, Pende D, Migone N, Gasorati G, Tambussi G, Moretta A, Moretta L (1988) Antigen recognition by human T cell receptor γ-positive lymphocytes: specific lysis of allogeneic cells after activation in mixed lymphocyte culture. J Exp Med 167: 1517
Egawa K, Tanino T (1982) Nonspecific cytotoxic cells induced in vivo and their comparison to culture-induced cytotoxic cells. Jpn J Exp Med 52: 237
Faure F, Jitsukawa S, Miossec C, Hercend T (1990) CD1c, as a target structure for human T lymphocytes: analysis with peripheral blood γ/δ cells. Eur J Immunol 20: 703
Hall RE (1985) A monoclonal antibody (RH1-38) which inhibits multiple systems of cell mediated cytotoxicity: I. Identification of a novel epitope on a killer cell surface bimolecular complex important in the cytotoxic response. Mol Immunol 22: 757
Haregervoin A, Soman G, Hom RC, Finberg RW (1989) Human γδ+ T cells respond to mycobacterial protein. Nature 340: 309
Hera A, Toribio ML, Marquez C, Martinez-A C (1985) Interleukin 2 promotes growth and cytolytic activity in human T3+4−8− thymocytes. Proc Natl Acad Sci USA 82: 6268
Hercend T, Reinherz EL, Meuer S, Schlossmann SF, Ritz J (1983) Phenotypic and fuctional heterogeneity of human cloned natural killer cell lines. Nature 301: 158
Ito H, Kaer LV, Bonneville M, Hsu S, Murphy DB, Tonegawa S (1990) Recognition of the product of a novel MHC TL region gene (27b) by a mouse γδ T cell receptor. Cell 62: 549
Itohara S, Nakanishi N, Kanagawa O, Kubo R, Tonegawa S (1989) Monoclonal antibodies specific for native murine T-cell receptor γδ: Analysis of γδ T cells during thymic ontogeny and in peripheral lymphoid organs. Proc Natl Acad Sci USA 86: 5094
Kiyohara T, Tanino T, and Egawa K (1982) T cell-dependent nonspecific cytotoxicity induced by culture of mouse spleen cells against natural killer-insensitive tumor cells. Jpn J Exp Med 52: 201
Kozbor D, Trinchieri G, Monos DS, Isobe M, Russo G, Haney JA, Zimijewski C, Croce CM (1989) Human TCR-γ+/δ+, CD8+ T lymphocyte recognize tetanus toxoid in an MHC-restricted fashon. J Exp Med 169: 1847
Kubo RT, Born W, Kappler JW, Marrack P, Pigeon M (1989) Characterization of a monoclonal antibody which detects all murine αβ T cell receptors. J Immunol 142: 2736
Markgoba MW, Sanders ME, Ginther Luce GE, Dustin ML, Springer TA, Clark EA, Mannoni P, Shaw S (1988) ICAM-1, a ligand for LFA-1-dependent adhesion of B, T and myeloid cells. Nature 331: 86
Matis LA, Fry AM, Cron RQ, Cotterman MM, Dick RF, Bluestone JA (1989) Structure and specificity of a class II MHC alloreactive γ/δ T cell receptor heterodimer. Science 245: 746
Terhorst C, Bleicher PA (1989) Recognition of cluster of differentiation 1 antigen by human CD4−CD8− cytotoxic T lymphocytes. Nature 341: 447
Rivas A, Koide J, Cleary ML, Engleman EG (1989) Evidence for involvement of the γ/δ T cell antigen receptor in cytotoxicity mediated by human alloantigen-specific T cell clones. J Immunol 142: 1840
Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA (1984) Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res 44: 1946
Seo N, Okazaki T, Nakanishi-Ito C, Tanino T, Matsudaira Y, Takahashi T, Egawa K (1992) Expression of the Qa-2k phenotype encoded by the Q5k gene on the surface of tumor cells derived from H-2k mice. J Exp Med 175, 547
Stanton TH, Boyse EA (1976) A new serologically defined locus, Qa-1, in the Tla-region of the mouse. Immunogenetics 3: 525
Tanino T, Seo N, Okazaki T, Nakanishi-Ito C, Sekimata M, Egawa K (1992) Detection of allogeneic Qa/TL and Ly specificities on murine tumor cells with IgD in tumor regressor serum. Cancer Immunol Immunother 35: 230
Vernachio J, Li M, Donnenbery AD, Soloski MJ (1989) Qa-2 expression in the adult murine thymus. A unique marker for a thymic subset. J Immunol 142: 48
Vidovic D, Roglic M, McKune K, Guerder S, McKay C, Dembic Z (1989) Qa-1 restricted recognition of foreign antigen by γ/δ T cell hybridoma. Nature 340: 646
Waneck GL, Sherman DH, Clavin S, Allen H, Flavell RA (1987) Tissue-specific expression of cell-surface Qa-2 antigen from a transfected Q7b gene of C57BL/10 mice. J Exp Med 165: 1358
Wigler M, Pellicer A, Silverstein S, Axel R, Urlaub G, Chasin L (1979) DNA-mediated transfer of the adenine phosphoribosyl transferase locus into mammalian cells. Proc Natl Acad Sci USA. 76: 1373
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Okazaki, T., Nakanishi-Ito, C., Seo, N. et al. Recognition of the Qa-2k tumor antigen by T cell receptor γ/δ of an immunopotentiator-induced tumoricidal T cell of mice. Cancer Immunol Immunother 36, 83–88 (1993). https://doi.org/10.1007/BF01754406
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DOI: https://doi.org/10.1007/BF01754406