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L E Samelson

Publications and source records attributed to L E Samelson.

117 records · Page 7Linked to original sources
PubMed1983

T cell clone-specific alloantisera that inhibit or stimulate antigen-induced T cell activation.

Pigeon cytochrome c-specific, IL 2-secreting T cell hybrids have been used for immunizations to generate alloantibodies against the T cell antigen receptor on these cells. The B10.A-derived cloned T cell hybrid 2B4 was emulsified in complete Freund's adjuvant and injected i.p. into several F1 strains of mice. After boosting the recipient animals with cells in incomplete Freund's adjuvant, malignant ascites developed. In the (BALB/c X AKR)F1 or (AKR X BALB/c)F1 strains, these ascites consistently contained material that specifically inhibited the antigen-induced IL 2 secretion of only the immunizing 2B4 cell. The inhibitory material was antibody that specifically bound and could be absorbed only by 2B4. A similar immunization was performed with the cell 2C2. Although this cell apparently has similar antigenic fine specificity as 2B4, high concentrations of ascites generated by 2C2 immune animals inhibited antigen-induced IL 2 release only from 2C2. At lower concentrations of ascites, this preparation synergized with antigen to increase the IL 2 release, again only from 2C2. This antibody preparation did not affect concanavalin A-induced IL 2 release. The most likely explanation for these data is that the ascites contain antibodies that react with the antigen-specific receptor on the T cell hybrids.

Animals↗
PubMed1982

The fine specificity of antigen and Ia determinant recognition by T cell hybridoma clones specific for pigeon cytochrome c.

The activation of proliferative T lymphocytes normally involves the simultaneous recognition of a particular foreign antigen and a particular Ia molecule on the surface of antigen-presenting cells, the phenomenon of major histocompatibility complex (MHC) restriction. An analysis of T cell clones specific for pigeon cytochrome c, from B10.A and B10.S(9R) strains of mice, revealed the unusual finding that several of the clones could respond to antigen in association with Ia molecules from either strain. Using these cross-reactive clones, we performed experiments which demonstrated that both the Ia molecule and the T cell receptor contribute to the specificity of antigen recognition; however, MHC-linked low responsiveness to tuna cytochrome c (an immune response gene defect) could not be attributed solely to the efficacy with which the Ia molecules associated with the antigen. These results imply that antigen and Ia molecules are not recognized independently, but must interact at least during the process of T cell activation.

Animals↗
PubMed1977

Selective response to H-Y antigen by F1 female mice sensitized to F1 male cells.

T-cell mediated cytotoxic responses to H-Y antigen require co-recognition of H-Y and H-2 gene products. F1 mael stimulating cells and target cells express H-Y antigen in association with both parental H-2 haplotypes. However, F1 females primed in vivo and challenged in vitro with F1 male cells lyse male target cells of F1 and only one parental H-2 haplotype. Thus, (CBA X B10)F1 females sensitized to (CBA X B10)F1 male cells lyse (CBA X B10)F1 and CBA but not B10 male target cells, and (BALB/c X B10)F1 females sensitized to (BALB/c X B10)F1 male cells will lyse (BALB/c X B10)F1 and B10 but not BALB/c male target cells. It is suggested that this may represent an effect of immune response or suppressor genes mapping in the major histocompatibility gene complex which regulate responsiveness to H-Y antigen.

Animals↗
PubMed1976

The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.

Animals↗
PubMed1975

In vitro cell-mediated immune responses to the male specific(H-Y) antigen in mice.

C57BL/10 female mice were primed to the male specific antigen H-Y, either by grafting with syngeneic male tail skin or by i.p. injection of syngeneic male spleen cells. Primed female spleen cells, either unseparated or filtered through nylon wool to remove most of the B lymphocytes, were then cultured for 5 days in vitro with irradiated syngeneic male spleen cells and assayed against 51Cr-labeled target cells. Both unseparated and nylon wool filtered female cells displayed significant cytotoxic activity restricted to male target cells. Pretreatment of sensitized female cells with antitheta serum and complement just before assay abolished cytotoxic responses. We were unable to demonstrate cell-mediated cytotoxic responses into two nonresponding strains, CBA and B10.A, which fail to reject male isografts. The cytotoxic activity of C57BL/10 female cells was restricted to male target cells histocompatible with C57BL/10 over at least a portion of the major (H-2) histocompatibility complex. We conclude that secondary in vitro cytotoxic responses against the H-Y antigen are mediated by cytotoxic T lymphocytes, and that the H-Y target cell antigen may be specified by the H-2 complex.

Animals↗
PubMedDate not supplied

Expression of genes of the T-cell antigen receptor complex in precursor thymocytes.

The antigen receptor on T lymphocytes has recently been characterized as a heterodimeric, transmembrane glycoprotein consisting of disulphide-linked alpha (acidic) and beta (basic) subunits of relative molecular mass (Mr) 40,000-45,000 each. The genes encoding these proteins have been cloned and shown to resemble immunoglobulin genes in both overall structure and the requirement for DNA rearrangement before expression. In humans, three additional proteins, termed the T3 complex, are found associated with the clonotypic receptor, and a role for T3 in receptor expression has been proposed. Despite these recent advances in characterizing the antigen receptor complex, there is as yet little understanding of T-cell maturation, particularly the stage of T-cell ontogeny at which the genes encoding the antigen receptor and its associated structures are expressed and assembled. In the adult, stem cells destined to differentiate into T cells arise in the bone marrow and migrate to the thymus, where T-cell precursors proliferate, develop a preference for recognizing antigens in the context of self MHC molecules and are released to the periphery. Recently, cells that have the properties of immature murine thymocytes have been isolated and described. We have now analysed these cells with a series of molecular probes and we describe three distinct patterns of T-cell antigen receptor gene rearrangements in developing thymocytes.

Animals↗
PubMedDate not supplied

A new subunit of the human T-cell antigen receptor complex.

The T-cell antigen receptor binds antigen in association with a cell surface molecule encoded by the major histocompatibility complex (MHC). MHC restricted recognition of antigen by this receptor leads to the complex pattern of programmed gene expression that characterizes T-cell activation. The eventual understanding of human T-cell function will require the complete elucidation of the structure of the human T-cell antigen receptor. On human T cells, clonally determined, disulphide-linked alpha and beta chains of the receptor are non-covalently and stoichiometrically associated with three additional polypeptides known as the T3 complex. These receptor subunits are glycoproteins of relative molecular mass (Mr) 25,000 (25K) and 20K (gamma and delta) and a non-glycosylated 20K protein (epsilon). Our studies of murine T cells show that the mouse T-cell antigen receptor consists of at least seven distinct polypeptide chains. In addition to clonotypic alpha and beta chains, the murine complex consists of glycoproteins of 26K and 21K and endoglycosaminidase F (endo F)-insensitive polypeptides of 25K, 21K and 16K. The latter, which we have termed zeta (zeta), exists as a homodimer within the complex. The 26K component (gp26) has been shown to be the murine analogue of the human delta chain. Other cross species homologies remain to be established, however none of the described human receptor components appear similar to the murine zeta polypeptide. We report here the use of an antiserum raised against the murine zeta subunit to identify a previously unrecognized component of the human T-cell antigen receptor. This human protein is T-cell specific and biochemically similar to the murine zeta polypeptide.

Animals↗
PubMedDate not supplied

Abnormal tyrosine phosphorylation on T-cell receptor in lymphoproliferative disorders.

The study of human autoimmune diseases has benefited greatly from analysis of animal models. Mice that are homozygous for either the lpr (lymphoproliferation) or gld (generalized lymphoproliferative disease) mutant genes develop a disease characterized by massive lymphadenopathy and autoantibody formation. With age, the lymphoid organs in these mice are replaced with a greatly expanded population of abnormal lymphocytes. Recent work has shown that these cells are likely to be in the T-cell lineage. They rearrange and transcribe the genes for the alpha and beta subunits of the T-cell receptor (TCR) and a third, T-cell receptor-like gene, T gamma. As determined by immunofluorescence with anti-receptor antibodies the cells also express TCR on the cell surface. The murine T-cell receptor consists of the alpha and beta chains, derived from the rearranged alpha and beta genes, in non-covalent association with seven other chains; the delta chain, of relative molecular mass (Mr) 26,000 (26K), the epsilon chain (25K), a glycosylated 21K chain (gp21) which is probably the homologue of the gamma chain of T3 (CD3), a 16K homodimer (zeta) and a 21K dimer (p21). This multichain complex is thought to be the murine analogue of the human T3 complex. After activation of normal T cells by antigen or lectin, p21 is phosphorylated on tyrosine residues and gp21 is phosphorylated on serine residues. In contrast, in the gld and lpr cells, p21 is phosphorylated even in the absence of antigen or lectin, whereas gp21 is not phosphorylated.

Amino Acids↗