Production of a monoclonal allo‐antibody to murine natural cytotoxic cells

Abstract

Summary A mouse IgGi monoclonal antibody (1C4), which recognizes a cell surface molecule on murine natural cytotoxic{NC) cells was produced. By flowcytometry. IC4preferentially reacted with less than 5% of fresh CBA spleen cells and 20-50% of CBA-interleukin-3 (lL-3) cells, an in vitro derived NC-like cell line. In vitro treatment of spleen cells from a number of inbred mouse strains either with 1C4 alone or 1C4 coupled to dynabeads markedly decreased or abolished NC activity of the cells against ^'Cr-labelled WEHl-164 targets. Splenic NC activity of these same mouse strains was also reduced or abolished by in vivo administration of IC4. The effect was evident within 2 h of treatment and persisted for at least I week. In contrast IC4 had little or no effect on splenic NK activity against "Cr-labeiled YAC-I targets over the same range of experiments in vitro and in vivo. Results of strain surveys for both in vitro and in vivo reduction of splenic NC activity by 1C4 treatment showed that CBA. C57BL/6, BALB/c and NZB mice were positive and CE and DBA/2 mice were negative, indicating that 1C4 recognizes an allo-antigen on mouse NC cells. This allo-antibody has been designated NC-II, and thus IC4 is an anti-NC-11 monoclonal antibody.

Natural Cytotoxicity of NC‐2+ Cells Against the Growth and Metastasis of WEHI‐164 Fibrosarcoma

“…Further cellular, functional and biochemical data 88 Natural Cytotoxicity of NC-2 + Cells indicated that NC-2 is not the same receptor as the NC-1.1 receptor identified by moAb 1C4 on cells mediating NC. Mice rendered NC deficient by injection of mAb 1C4 showed reduced tumour surveillance when compared to control mice [20,22]. The in vitro data obtained for mAb D9 suggested that its injection into mice in vivo would also deplete splenic NC.…”

“…Mice rendered NC deficient by injection of mAb 1C4 showed reduced tumour surveillance when compared to control mice [20, 22]. The in vitro data obtained for mAb D9 suggested that its injection into mice in vivo would also deplete splenic NC.…”

“…To our knowledge, only two receptors, NC‐1.1 [20] and NC‐2 [21], have been identified on murine leucocytes, which mediate NC against WEHI‐164 (NC‐sensitive target) whilst the activity of these cells against NK‐sensitive target (YAC‐1 tumour cells) was not affected. Studies showed that mice rendered deficient in NC by the administration of the anti‐NC‐1.1 mAb 1C4 have accelerated growth of a number of transplantable tumours [22] and exhibited increased susceptibility to chemical carcinogens [23] compared to control mice.…”

LY-6C+ natural T (NT) cells mediate immune surveillance against NK-sensitive and NK-resistant transplantable tumours in certain strains of mice

“…--Lytic units (LU) were derived from the linear slope of the graph of percent specific lysis vs. E:T ratio (Smart et al, 1990 DAY ANIMALS SACRIFICED FIGURE 3 -Sustained reduction of splenic NK in BALB/c mice treated with repeated injections of MAb 2B6-F2. Groups of 3 BAL,B/c mice were injected i.p.…”

“…Cells mediating NK or NC in mice can be identified by allo-receptors NK-1.1 (Ryan et al, 1992) and NC-1.1 (Smart et al, 1990;Brien et al, 1994), respectively. Direct evidence for the role of NK-1.1+ and NC-1.1+ cells in tumour immunosurveillance has been provided by the accelerated growth of certain transplantable tumours in mice depleted of these cells (Seaman et al, 1987;Smart et al, 1992).…”