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L A Manson

Publications and source records attributed to L A Manson.

17 recordsLinked to original sources

Does antibody-dependent epitope masking permit progressive tumour growth in the face of cell-mediated cytotoxicity?

It is not clear how immunogenic tumours can grow from small inocula in syngeneic hosts that mount both T-cell and B-cell responses. In this article Lionel Manson argues that antibody coats the tumour cells, protecting them from attack by cytotoxic lymphocytes, and thus permits the tumour to continue to grow and overwhelm the host. These observations may explain the paradox that an immunogenic tumour overwhelms the tumour-bearing host in the face of an ongoing anti-tumour immune response.

Animals

A subset of normal human B lymphocytes expresses an antigen cross-reactive with gp52 of murine mammary tumor virus.

Three monoclonal antibodies (MAbs), VE7, VIG3, and IXF9, that detect the 52-kd glycoprotein (gp52) of murine mammary tumor virus (MMTV) were tested for reactivity on normal human tonsillar lymphoid cells in an indirect immunofluorescence assay. Two of the MAbs, VE7 and VIG3, reacted with subpopulations of B cells, whereas the third MAb, IXF9, showed only very low-level reactivity with human lymphoid cells. VE7 and VIG3 also reacted with small populations of peripheral blood lymphocytes, and all three MAbs reacted with some transformed human cell lines. The data suggest that subpopulations of normal human lymphocytes express antigens that are cross-reactive with the MMTV gp52, although not all of the viral gp52 epitopes are expressed on the surface of these cells.

Antibodies, Monoclonal

Novel tumor-specific antigen(s) response observed in a syngeneic lymphoma-bearing host.

Immunoglobin (Ig) has been found to accumulate on P815Y (H-2d) and L5178Y (H-2d) tumor cells during progressive growth in syngeneic host DBA/2 mice. Density of the accumulated Ig per cell increases as the tumor grows while the tumor cells become resistant to lysis by ascitic syngeneic cytotoxic cells. Tumor cells grown in vivo coated with this specific Ig no longer bind significant amounts of antibodies against H-2D and H-2K antigens. The membrane-bound Ig reacts with a rabbit antimouse Fab and a rabbit antimouse IgM reagent, but it does not react with a rabbit antimouse IgG or IgA reagent. It binds specifically to tumor cell lines that are sensitive to the ascitic cytotoxic cells but not to resistant tumor cell lines. The membrane-bound Ig can be eluted from tumor cells with 3 M NaSCN or 0.2 M acetic acid. Binding studies indicate that this eluted Ig is not an anti-H-2D/K antibody, yet it immunoprecipitates H-2D/K antigens from NP40 lysates of P815Y cells. It is proposed that the Ig is directed against a tumor antigen that is physically associated with the H-2D/K antigens of the tumors.

Animals

Immunological analysis of A strain mice bearing the A-10 mammary adenocarcinoma.

The present investigation was undertaken to determine whether antitumor antibodies are produced by A strain mice during the growth of a transplantable mammary adenocarcinoma (A-10). The antibody response was monitored by a sensitive radioimmunoassay which can detect 1 ng of antibody. No evidence of a humoral antitumor response was observed in animals given i.p. or s.c. injections of A-10 ascites cells. Control experiments showed that a humoral response was detectable 1 week after the inoculation of an allogeneic tumor. Immunoglobulin binds nonspecifically to cells via an Fc portion of the immunoglobulin molecule, and this was seen with a tumor bearer serum pool and with immunoglobulin preparations eluted from A-10 ascites cells. No specific antitumor antibody was found in these sources. The A strain mice could not be immunized to reject a challenge of live A-10 cells with mitomycin C-treated A-10 cells, with neuraminidase-treated A-10 cells, or with A-10 membrane preparations. It was concluded that the A-10 tumor is not immunogenic in its host of origin.

Adenocarcinoma

Intracellular localization and immunogenic capacities of phenotypic products of mouse histocompatibility genes.

The transplantation antigens are the phenotypic products of genes which control histocompatibility in vertebrate species. The products of major histocompatibility locus of the mouse, H-2, have been studied as a model. The H-2 transplantation antigens are expressed on cellular membranes in all tissues examined. These gene products have been isolated from cells associated with subcellular membranes. These membranes have been assayed both for their antigen content (antigenicity) and for their capacities to induce a primary humoral and a cell-mediated response (immunogenicity). In all tissues examined, the H-2 antigens (products of the K and D regions of H-2) were found expressed in high concentration on cell surface membrane. However, immunogenic activity was observed only with spleen and thymus preparations, consisting mainly of intracellular membranes (MLP). Immunogenic MLP was also isolated from lymphoblast and fibroblast cells, and again was derived mainly from endoplasmic reticulum. In other tissues, such as liver, kidney, and erythrocytes, H-2 antigens were found only on surface membrane and in an antigenic but nonimmunogenic form. A novel method for tagging surface membrane of mammalian cells is presented. It consists of binding, to whole cells in a covalent linkage, purified preparations of the beta-galactosidase of E. coli. The bound enzyme has proved to be an unambiguous marker for surface membrane. With this marker, the stability of surface membrane to shear forces during homogenization could be assessed. A number of considerations suggest that immunogenicity of transplantation antigens may be due to factor(s) present on the membranes in addition to the H-2 antigenic determinants. There are indications that these factors may be controlled by the I region of the H-2 complex. It is interesting to note that normal tissues which have Ia antigens on their surface membranes yield immunogenic MLP (spleen and thymus), whereas those without Ia surface antigens yield an antigenic MLP that has no immunogenic capacity (liver, kidney, and erythrocytes).

Animals

A radioimmunoassay for antibodies against surface membrane antigens using adhering cells.

A radioimmunoassay using cells adhering to plastic is described. In this assay, A-10 mammary carcinoma attached to the surface of plastic in microtiter plates were permitted to bind antibody and the bound antibody was detected with purified rabbit 125I-anti-mouse-Fab. The bound radioactive material was eluted with glycine-HCI buffer (pH 2.5), and the acid eluates were counted in a gamma counter. This assay can be used to detect cytolytic or noncyctolytic antibody to cell surface antigens in studies with any tumor or normal cell that will adhere to a solid surface.

Adenocarcinoma

Obituary.

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Histocompatibility

Induction of the immune response to cell surface antigens in vitro.

Two tissue culture incubation systems are described in which immune responses to cell surface antigens have been demonstrated. In the one-way "mixed lymphocyte interaction" system, a specific stimulation of thymidine uptake was induced by a particulate membrane antigen fraction, the microsomal lipoproteins (MLP), when low levels (0.01 to 0.001 mug per ml) were incubated with spleen or lymph node cells from nonsensitized mice. No stimulation was seen when allogeneic MLP was used at high levels, 10 mug per ml, nor at any level with syngeneic MLP. Specific effectors were demonstrated after 72-hr incubation with stimulatory levels of allogeneic MLP in three separate in vitro assays, a plaque-forming cell reduction assay, a tumor target assay, and an antigen-binding cell assay. In the latter assay, [125I]MLP was used as the source of antigen. This system has limited potential inasmuch as mouse spleen cells do not survive in it beyond the 4th day of culture. The second tissue culture system, the Marbrook system, has much greater possibilities because at least 25% of the inoculum is recovered 7 days later. In this culture system a cell-free sheep erythrocyte membrane preparation can induce plaque-forming cells in the absence of macrophages. Using a sensitive radioimmunoassay, free specific antibody was detected in culture supernatant fluids. With the same culture system, allogeneic lymphocytotoxic cells (killer) have been induced with spleen cells from unprimed mice in strains differing at the major histocompatibility locus (H-2). Allogeneic MLP induced very significant "killer" cell activity with spleen cells from primed mice. In a syngeneic tumor system, significant amounts of killer cell activity were induced with unprimed spleen cell inocula, and much larger amounts induced with spleen cells from immunized mice.

Animals