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Biomedical subjects

R C Nowinski

Publications and source records attributed to R C Nowinski.

At least 37 records · Page 2Linked to original sources

Thy-2: a murine thymocyte-brain alloantigen controlled by a gene linked to the major histocompatibility complex.

We describe a new murine cell-surface alloantigen, provisionally designated Thy-2, which is expressed primarily on thymocytes and brain tissue. Although Thy-2 is also expressed at lower levels on bone-marrow and spleen cells, this antigen does not appear to be present on lymph-node, liver, or red blood cells. Immunoprecipitation of surface-labeled thymocyte extracts from a variety of inbred strains reveals this antigen to be a single polypeptide of 150000 daltons. Quantitative membrane immunofluorescence demonstrates that Thy-2 is a minor cell-surface component which is present on the majority of thymocytes. Mice heterozygous at the Thy-2 locus express approximately 50 percent as much antigen as positive homozygotes. Expression of the Thy-2 alloantigen is controlled by a single semidominant gene located approximately 3 cM to the right of the H-2K locus on chromosome 17.

Absorption↗

Monoclonal antibodies recognizing normal human T lymphocytes and malignant human B lymphocytes: a comparative study.

We have undertaken a direct comparison of 8 different murine monoclonal antibodies that recognize antigens shared by human T cells and certain malignant B cells. Immune precipitation, lysostripping, and competitive binding experiments indicate that the antigenic determinants detected by antibodies Leu 1, T101, 17F12, SC1, A50, OKT1, and 10.2 are closely associated on the same molecular species and may in fact be identical. The antigenic determinant recognized by antibody 12.1, which has properties similar to the 1 detected by other antibodies, is present on a distinct cell-surface molecule. Our results emphasize the importance of a quantitative direct comparison of different monoclonal antibodies in distinguishing newly reported antibodies from those already described. Such a comparison can resolve apparent discrepancies that arise either from methodologic variations or from differences in antibody avidity.

Animals↗

Mouse leukemia: therapy with monoclonal antibodies against a thymus differentiation antigen.

Monoclonal antibodies against a thymus cell differentiation antigen (Thy-1.1) were effective in the therapy of a transplanted mouse leukemia. Passive immunization resulted in high titers of cytotoxic antibody in the serum of treated mice and the suppression of metastatic tumor cells. The tumor-suppressive effects of the monoclonal antibodies were amplified by the administration of exogenous complement. This combined antibody and complement therapy resulted in the cure of leukemia in a significant proportion of the treated animals.

Animals↗

A new human T-cell differentiation antigen: unexpected expression on chronic lymphocytic leukemia cells.

Monoclonal antibody 10.2 reacts with a monomorphic antigen expressed on the surface of virtually all thymocytes, as well as thymus-dependent lymphocytes in the peripheral blood and bone marrow. In contrast, antibody 10.2 did not react with normal peripheral blood B cells, monocytes, or the non-T-cell fraction of bone marrow. This complement fixing IgG2a antibody also reacted with established leukemic T-cell lines, but not with cell lines of either normal or malignant B-cell origin. Similarly, when tested against acute leukemia blasts, the 10.2 antibody reacted with those from patients with T-cell acute leukemia, but not with those from patients with acute null cell or non-lymphocytic leukemia. An unexpected exception to this pattern was the reaction of 10.2 antibody with leukemic cells from patients with B-cell type chronic lymphocytic leukemia. Immune precipitates formed with 10.2 antibody and detergent lysates of radiolabeled T-cells contained three polypeptides with molecular weights of 65 000, 55 000, and 50 000 daltons. It has not been determined whether all three of these polypeptides contain the 10.2 antigenic determinant, or whether these proteins represent a multimeric antigen complex.

Antibodies, Monoclonal↗

Monoclonal antibodies identify individual determinants on mouse mammary tumor virus glycoprotein gp52 with group, class, or type specificity.

Hybrid cell lines producing monoclonal antibodies against the C3H strain of mouse mammary tumor virus (C3H MMTV) were prepared by the fusion of mouse myeloma cells with the lymphocytes of BALB/c mice that were immunized with C3H MMTV. Approximately 10% of the hybrid cells initially plated after cell fusion produced immunoglobulins that reacted in antibody-binding assays with C3H MMTV; 40 of these cells were cloned, and 6 eventually yielded stable cell lines. High concentrations of monoclonal antibodies (5 to 20 mg/ml) were obtained from serum and ascites fluid of syngeneic mice inoculated with the hybrid cells. All of the monoclonal antibodies were directed against the envelope glycoprotein gp52. Three of the hybrid cell lines produced immunoglobulins of the immunoglobulin M subclass and three produced immunoglobulin G2a. The monoclonal antibodies showed limited charge heterogeneity in light and heavy chains when analyzed by high-resolution, two-dimensional gel electrophoresis. Three serologically distinct specificities were observed when these ascites fluids were tested against different strains of MMTV. The antigenic determinants detected were the following: (i) a type-specific determinant unique to the C3H strain of MMTV; (ii) class-specific determinants shared between C3H and GR MMTVs; and (iii) a group-specific determinant found on C3H, GR, RIII, and the endogenous C3H (C3Hf) MMTVs. Because monoclonal antibodies recognize single antigenic determinants, these results demonstrate for the first time that the three patterns of antigenic reactivity for MMTV are related to individual determinants on the gp52 molecule and also clearly show that one strain of MMTV can be distinguished from other strains.

Animals↗

Cytotoxic activities of monoclonal antibodies against the envelope proteins of murine leukemia virus.

Monoclonal antibodies against the envelope proteins [gp70 and p15(E)] of murine leukemia virus react with the cell surface of virus-infected cells. The specificity and potency of these antibodies exceed those observed with conventional polyvalent antisera. In cytotoxic assays, certain of the monoclonal anti-gp70 antibodies demonstrate 1000-fold differences in their titer on leukemic and normal thymus cells.

Animals↗