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Biomedical subjects

M Kimoto

Publications and source records attributed to M Kimoto.

At least 199 records · Page 11Linked to original sources
PubMed1981

Major histocompatibility complex-restricted antigen presentation to antigen-reactive T cells by B lymphocyte tumor cells.

Previous reports have demonstrated that accessory cells function to present soluble protein antigens in association with gene products encoded within the I region of the major histocompatibility complex (MHC) to antigen-reactive T helper cells. The biochemical events that occur during antigen presentation are, however, not well-documented primarily because of the difficulties involved in purifying sufficient numbers of homogeneous antigen-presenting cells. In this paper, a number of Ia-positive B lymphocyte tumor lines are shown to be capable of presenting soluble protein antigens to antigen-reactive continuous T cell lines in an MHC-restricted fashion. The characterization of the antigen presentation function of these tumor cells indicates that the tumor cells have many of the functional antigen-presenting characteristics previously thought to be limited to macrophages. These tumor cells should provide a useful model system for determining the biochemical events that occur in antigen uptake and processing as well as for determining the potential interactions between processed antigen and Ia molecules on the plasma membrane of these antigen-presenting cells.

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PubMed1981

Antigen-reactive T clones. III. Low responder antigen-presenting cells function effectively to present antigen to selected T cell clones derived from (High Responder x Low Responder)F1 mice.

Long-term-cultured poly(Tyr, Glu)-poly-D,L,-Ala-poly-Lys [(T,G)-A--L]-reactive T cells and clones derived from (high responder x low responder)F1 [(C57BL/6 x A/J)F1] mice were shown to recognize (T,G)-A--L presented by cells from low responder strain A/J mice. The antigen-presenting determinant(s) that allowed recognition of (T,G)-A--L by such T cell clones was controlled by the I-A subregion of the major histocompatibility complex. These results suggest that there is no functional defect in the ability of low responder Ir gene products (I-A antigens) to associate with (T,G)-A--L for effective recognition by T cells. Although these results might tentatively be interpreted to suggest that Ir gene-controlled low responsiveness is due to the inability of the T cell to recognize the association between (T,G)-A--L and low responder I-A gene products, it is similarly possible that there might be a defect in the functional capabilities of low responder antigen-presenting cells to effectively process (T,G)-A--L into immunodominant epitopes.

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PubMed1981

Antigen-reactive T cell clones. II. Unique homozygous and (high responder x low responder)F1 hybrid antigen-presenting determinants detected using poly(Tyr, Glu)-poly D, L-Ala--poly Lys-reactive T cell clones.

Using murine (T,G)-A--L-reactive T cell clones, we have demonstrated the existence of unique homozygous antigen-presenting determinants expressed on C57bl/6 mice, controlled by the I-A subregion of the murine major histocompatibility complex (MHC), which are not expressed on semisyngeneic (C57Bl/6 x A/J)F1 [(B6A)F1] cells. Additionally, we were able to demonstrate that there exist (T,G)-A--L-reactive clones in F1 mice derived between low responder and high responder parents [(B6A)F1] that recognize antigen in association with transcomplementing hybrid I-A subregion determinants expressed uniquely on (B6A)F1 cells not expressed on cells of either of the parental strains. These data suggest that phenotypic high responsiveness exhibited by (higher responder x low responder)F1 mice was not simply controlled by the high responder parental genome, but was controlled at the phenotypic level of expression of antigen-presenting determinants. Such antigen-presenting determinants can be created by complementation using products of the low responder as well as high responder genome. The significance of the existence of such F1 specific hybrid antigen-presenting determinants for T cell specificity and recognition of self was discussed.

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PubMed1981

Functional helper activity of monoclonal T cell populations: antigen-specific and H-2 restricted cloned T cells provide help for in vitro antibody responses to trinitrophenyl-poly(LTyr,Glu)-poly(DLAla)--poly(LLys).

The ability of long-term cultured and monoclonal T cell populations to provide antigen-specific help was assessed in a system of Ir gene-controlled in vitro antibody responses to soluble antigens. T-cell colonies and monoclonal T-cell lines were generated which proliferated specifically in response to poly(LTyr,Glu)-poly(DLAla)--poly(LLys) [(T,G)-A--L] and were I-A restricted in these proliferative responses. These (T,G)-A--L-specific T-cell populations were evaluated for their ability to help unprimed and T-cell depleted spleen cell populations in the generation of antibody responses to trinitrophenyl (TNP)-(T,G)-A--L in vitro. It was found that long-term T-cell lines, including monoclonal T-cell populations derived by limiting dilution, were highly efficient helper cells for IgM responses to TNP-(T,G)-A--L. These helper T cells were both antigen-specific and I-A restricted in their ability to be activated and to cooperate with T-cell depleted spleen cell populations. Once specifically activated, however, these clones provided help that was antigen nonspecific. These studies have thus demonstrated the ability of antigen-specific and H-2-restricted monoclonal T-cell populations to provide help for responses to soluble antigens in vitro.

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PubMed1981

Reconstitution of Ir genes, Ia antigens, and mixed lymphocyte reaction determinants by gene complementation.

By using clones of murine T cells reactive with alloantigens as well as soluble antigens, it has been possible to demonstrate that Ia antigens, Ir gene phenomena (defined as the ability of immune T cells to recognize antigen), and mixed lymphocyte reaction (MLR)-stimulating determinants encoded within the I-A subregion are different manifestations associated with same product. These studies utilized the I-Ab mutant mouse B6.C-H-2bm (bm12), whose defect in the normal expression of the cell surface products of the I-Ab subregion can be partially circumvented through trans-complementation by deriving hybrids between bm12 and mice expressing normal I-A subregion products. Such mice [e.g., (bm12 X B10.A)F1] express several serologically normal I-Ab products but have defects in certain I-A subregion gene products normally expressed on cells of H-2a X H-2b heterozygote mice that are used as restricting elements for antigen recognition by antigen-reactive T cell clones or recognized as alloantigens by alloreactive T cell clones. This defect in cell surface expression of certain normal I-Ab products on the mutant bm12 cells has allowed us to suggest that there exist trans-complementing products on H-2a X H-2b heterozygote mice consisting of Ab alpha Ak beta and Ak alpha Ab beta that restrict antigen recognition by cloned T cells, stimulate MLR responses by cloned T cells, and react with certain anti-Ia antisera.

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PubMed1980

Antigen-reactive T cell clones. I. Transcomplementing hybrid I-A-region gene products function effectively in antigen presentation.

Studies in our laboratory and elsewhere have shown that it is possible to propagate antigen-specific murine T cells in vitro with resultant specific stepwise enrichment of antigen-induced proliferative cells. The proliferative responses of these T cells are antigen specific and dependent upon the presence of antigen-presenting cells (spleen cells) that share the I-A subregion with the proliferating T cell. Using techniques of soft-agar cloning, it has been further possible to isolate clones of antigen-reactive T lymphocytes from such long-term cultures. Data suggesting that these were clones of antigen-reactive T cells were obtained by studying the recognition of antigen in association with antigen-presenting cells with a panel of such clones of antigen-reactive T cells. Proof of clonality was obtained by subcloning. Clones derived from F1-immune mice can be divided into three separate categories: one clone recognizes antigen in association with antigen-presenting determinants of parent A and the F1; the second type recognizes antigen in association with antigen-presenting determinants of parent B and the F1; and the third type recognizes antigen only in association with antigen-presenting determinants of the F1 mouse. Genetic studies on the major histocompatibility complex requirements for antigen presentation to such F1-reactive T cell clones suggests that the hybrid antigen-presenting determinant in this system results from transcomplementation of products of the I-A region of haplotypes a and b. These studies support the concept developed in our laboratory that there exist unique F1 hybrid determinants on (A/J X C57BL/6) F1 cells and suggest that these determinants can be utilized physiologically by hybrid mice in immunocompetent cellular interactions.

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PubMed1978

Regulation of antibody response in different immunoglobulin classes. V. Establishment of T hybrid cell line secreting IgE class-specific suppressor factor.

Establishment of a mouse T hybrid cell line secreting suppressor factor(s) specific for the IgE antibody response is described. Fusion was made with polyethyleneglycol between AKR-derived T lymphoma cells (BW5147) and T cells from mice sensitized with DNP-Mycobacterium. Treatment of spleen cells with nondialyzable factor(s) in the culture supernatants of the T cell hybrid clone, 26-M10, showed a suppressive effect on IgE formation but not on IgG formation in adoptive transfer experiments. The suppressive effect was exerted through inactivation of normal or antigen-primed B cells responsible for IgE formation. It was also shown by direct cytotoxic test that the hybrid cells expressed H-2 and Thy-1 antigens derived from both parental cells on their surface. Karyotype analysis of the hybrid cells revealed that the number of chromosomes was less than the sum of the two parental cells' and the average was 50 (45 to 55). Although the 26-M10 hybrid cells lost the ability to secrete active suppressive factor(s) into culture medium 21 weeks after hybridization when the number of chromosomes in most of the cells was less than 41, recloning of the 26-M10 cells successfully recovered active suppressive clones.

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