Characterization of two monoclonal idiotype-binding suppressor T cell factors specific for the antibody response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). 1986

R Y Poon, and J A Kapp, and C W Pierce, and C M Sorensen

We have previously identified and described two distinct types of suppressor T cell factors specific for the PFC response to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) or L-glutamic acid50-L-tyrosine50 (GT). Both of these factors are antigen-specific and I-J+. GAT-TsF1 is not MHC-restricted and is composed of a single polypeptide chain, whereas GAT-TsF2 is MHC-restricted and is composed of two different polypeptide chains. We have not previously found evidence for an obligatory, idiotype-specific suppressor T cell in this suppressor pathway. However, we now report that idiotype-specific suppressor T cells can be elicited by exposing normal spleen cells to GAT-TsF1 or GAT-TsF2 in the absence of antigen in vitro. These factor (TsF1/TsF2)-induced cells have been fused with the AKR thymoma, BW5147, and hybridomas were selected for production of suppressor factors that inhibit GAT-specific antibody responses in vitro. In this report, we characterize one monoclonal factor from each fusion. Neither factor binds GAT or the related co-polymer, GT; both factors have binding sites for GAT-specific idiotypes but not for unrelated idiotypes either in the form of antibody immobilized on Sepharose or as cell surface determinants expressed by B cell hybridomas. Moreover, their reactivities for a panel of monoclonal anti-GAT antibodies are overlapping but not identical. Both factors are composed of two polypeptide chains, and both chains are required for suppressive activity; one chain bears the I-J determinant, whereas the other possesses the idiotype-binding activity of the intact molecule. Both idiotype-binding factors are restricted by MHC- and Igh-linked genes, and transcomplementation is observed in the F1 mice between MHC-congenic and Igh-congenic parents. Both factors are active late in Mishell-Dutton cultures. These data support the contention that these two factors are similar but nonidentical members of an anti-idiotypic class of GAT-specific suppressor factors.

UI MeSH Term Description Entries
D007108 Immune Tolerance The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc. Immunosuppression (Physiology),Immunosuppressions (Physiology),Tolerance, Immune
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
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D010455 Peptides Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS. Peptide,Polypeptide,Polypeptides
D011108 Polymers Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS). Polymer
D006825 Hybridomas Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure MONOCLONAL ANTIBODIES or T-cell products, identical to those produced by the immunologically competent parent cell. Hybridoma
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
D000911 Antibodies, Monoclonal Antibodies produced by a single clone of cells. Monoclonal Antibodies,Monoclonal Antibody,Antibody, Monoclonal
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D050378 T-Lymphocytes, Regulatory CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells. Regulatory T Cell,Regulatory T-Cell,Regulatory T-Lymphocyte,Regulatory T-Lymphocytes,Suppressor T-Lymphocytes, Naturally-Occurring,T-Cells, Regulatory,Th3 Cells,Tr1 Cell,Treg Cell,Regulatory T-Cells,Suppressor T-Cells, Naturally-Occurring,Tr1 Cells,Treg Cells,Cell, Regulatory T,Cell, Th3,Cell, Tr1,Cell, Treg,Cells, Regulatory T,Cells, Th3,Cells, Tr1,Cells, Treg,Naturally-Occurring Suppressor T-Cell,Naturally-Occurring Suppressor T-Cells,Naturally-Occurring Suppressor T-Lymphocyte,Naturally-Occurring Suppressor T-Lymphocytes,Regulatory T Cells,Regulatory T Lymphocyte,Regulatory T Lymphocytes,Suppressor T Cells, Naturally Occurring,Suppressor T Lymphocytes, Naturally Occurring,Suppressor T-Cell, Naturally-Occurring,Suppressor T-Lymphocyte, Naturally-Occurring,T Cell, Regulatory,T Cells, Regulatory,T Lymphocytes, Regulatory,T-Cell, Naturally-Occurring Suppressor,T-Cells, Naturally-Occurring Suppressor,T-Lymphocyte, Regulatory,Th3 Cell

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