Recognition of the Qa-2k tumor antigen by T cell receptor gamma/delta of an immunopotentiator-induced tumoricidal T cell of mice.
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 with P. 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 alpha 1 and alpha 2 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 from P. acnes-stimulated (C3H/He x 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 alpha 1/alpha 2 region of the Q7b gene product was demonstrated. The cytotoxic activity was dependent on T cells bearing T cell receptors of the gamma/delta type (TCR gamma/delta). The (C3H/He x 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 alpha 1/alpha 2 region of the Qa-2k tumor antigen by TCR gamma/delta.
Okazaki
T
T
Department of Tumor Biology, University of Tokyo, Japan.
Nakanishi-Ito
C
C
Seo
N
N
Tanino
T
T
Takiguchi
M
M
Egawa
K
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis*; D003602:Cytotoxicity, Immunologic; D006183:H-2 Antigens / Q000032:analysis*; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; C032907:Q surface antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta