The targeting of CD4+ T lymphocytes to a B cell lymphoma. A comparison of anti-CD3-anti-idiotype antibody conjugates and antigen-anti-idiotype antibody conjugates. 1989

M Gravelle, and A Ochi
Division of Molecular Immunology and Neurobiology, Mount Sinai Hospital Research Institute, Toronto, Ontario, Canada.

We have targeted CD4+ cytotoxic Th (Th/c) lymphocytes to a B cell lymphoma, through the use of a bispecific antibody containing binding sites for both the CD3 complex on the Th/c and the Id on the surface Ig of the B lymphoma (anti-CD3-anti-Id). Cloned, keyhole limpet hemocyanin (KLH)-specific Th/c cells were nonspecifically activated by the anti-CD3-anti-Id conjugate to lyse the Id+ B lymphoma A20-HL. This cytotoxicity was not inhibited by antibodies to CD4 or LFA-1 alpha molecules. The anti-CD3-anti-Id conjugates also induced non-lytic Th clones to become cytotoxic, a function not elicited when these cells were activated specifically by Ag. We compare this model to our previously described system where we targeted the KLH-specific Th/c cells to the Id+ B lymphoma A20-HL via a conjugate consisting of KLH covalently linked to the anti-Id antibody (KLH-anti-Id). The mechanism involved processing and presentation of KLH by the A20-HL target. This Ag-specific cytotoxicity was MHC class II restricted and was inhibited by antibodies to the CD4 molecule. In both systems, activation of the Th/c cells resulted in bystander killing of tumor but not normal targets. These results may have important implications for the use of Th/c cells in tumor immunotherapy.

UI MeSH Term Description Entries
D007130 Immunoglobulin Idiotypes Unique genetically-controlled determinants present on ANTIBODIES whose specificity is limited to a single group of proteins (e.g., another antibody molecule or an individual myeloma protein). The idiotype appears to represent the antigenicity of the antigen-binding site of the antibody and to be genetically codetermined with it. The idiotypic determinants have been precisely located to the IMMUNOGLOBULIN VARIABLE REGION of both immunoglobin polypeptide chains. Idiotypes, Immunoglobulin,Ig Idiotypes,Idiotype, Ig,Idiotype, Immunoglobulin,Idiotypes, Ig,Ig Idiotype,Immunoglobulin Idiotype
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D011948 Receptors, Antigen, T-Cell Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (CD3 COMPLEX). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains. Antigen Receptors, T-Cell,T-Cell Receptors,Receptors, T-Cell Antigen,T-Cell Antigen Receptor,T-Cell Receptor,Antigen Receptor, T-Cell,Antigen Receptors, T Cell,Receptor, T-Cell,Receptor, T-Cell Antigen,Receptors, T Cell Antigen,Receptors, T-Cell,T Cell Antigen Receptor,T Cell Receptor,T Cell Receptors,T-Cell Antigen Receptors
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003601 Cytotoxicity Tests, Immunologic The demonstration of the cytotoxic effect on a target cell of a lymphocyte, a mediator released by a sensitized lymphocyte, an antibody, or complement. AHG-CDC Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Tests,Microcytotoxicity Tests,Anti Human Globulin Complement Dependent Cytotoxicity Tests,Anti-Human Globulin Complement-Dependent Cytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Test,Antiglobulin-Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunologic,Cytotoxicity Tests, Anti-Human Globulin Complement-Dependent,Cytotoxicity Tests, Immunological,Immunologic Cytotoxicity Test,Immunologic Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin-Augmented,Lymphocytotoxicity Tests, Antiglobulin-Augmented,Microcytotoxicity Test,AHG CDC Tests,AHG-CDC Test,Anti Human Globulin Complement Dependent Cytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Test,Antiglobulin Augmented Lymphocytotoxicity Tests,Cytotoxicity Test, Immunological,Cytotoxicity Tests, Anti Human Globulin Complement Dependent,Immunological Cytotoxicity Test,Immunological Cytotoxicity Tests,Lymphocytotoxicity Test, Antiglobulin Augmented,Lymphocytotoxicity Tests, Antiglobulin Augmented
D004306 Dose-Response Relationship, Immunologic A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell. Immunologic Dose-Response Relationship,Relationship, Immunologic Dose-Response,Dose Response Relationship, Immunologic,Dose-Response Relationships, Immunologic,Immunologic Dose Response Relationship,Immunologic Dose-Response Relationships,Relationship, Immunologic Dose Response,Relationships, Immunologic Dose-Response
D006377 T-Lymphocytes, Helper-Inducer Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions. Helper Cell,Helper Cells,Helper T Cell,Helper-Inducer T-Lymphocytes,Inducer Cell,Inducer Cells,T-Cells, Helper-Inducer,T-Lymphocytes, Helper,T-Lymphocytes, Inducer,Helper T-Cells,Cell, Helper T,Cells, Helper T,Helper Inducer T Lymphocytes,Helper T Cells,Helper T-Cell,Helper T-Lymphocyte,Helper T-Lymphocytes,Helper-Inducer T-Cell,Helper-Inducer T-Cells,Helper-Inducer T-Lymphocyte,Inducer T-Lymphocyte,Inducer T-Lymphocytes,T Cell, Helper,T Cells, Helper,T Cells, Helper Inducer,T Lymphocytes, Helper,T Lymphocytes, Helper Inducer,T Lymphocytes, Inducer,T-Cell, Helper,T-Cell, Helper-Inducer,T-Cells, Helper,T-Lymphocyte, Helper,T-Lymphocyte, Helper-Inducer,T-Lymphocyte, Inducer
D006433 Hemocyanins Metalloproteins that function as oxygen transport proteins in the HEMOLYMPH of MOLLUSKS and ARTHROPODS. They are characterized by two copper atoms, coordinated with HISTIDINE residues, that reversibly bind a single oxygen molecule; they do not contain HEME groups. Hemocyanin,alpha-Haemocyanin,alpha-Hemocyanin,alpha-Hemocyanins,alpha Haemocyanin,alpha Hemocyanin,alpha Hemocyanins
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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