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Biomedical subjects

E S Vitetta

Publications and source records attributed to E S Vitetta.

At least 307 records · Page 17Linked to original sources
PubMed1977

B-cell tolerance. II. Trinitrophenyl human gamma globulin-induced tolerance in adult and neonatal murine B cells responsive to thymus-dependent and independent forms of the same hapten.

Neonatal splenic B cells which are responsive to thymus-dependent antigens (TD) are exquisitely susceptible to induction of tolerance (1,2). This state of tolerance is not mediated by suppressor T cells and is not a result of suboptimal macrophage function (1 and footnote one). In adult mice, induction of B-cell tolerance is not achieved with doses of antigen 1,000-fold higher (1) than those required to produce the same degree of unresponsiveness in neonates. In contrast to these results, studies with T-independent (TI) antigens indicate that neonatal and adult splenic B cells are equally susceptible to tolerance induction (3,4). However, such studies have not ascertained whether the neonate is more resistant to tolerance induction or the adult is hypersusceptible, i.e., does the induction of tolerance in cells responsive to TI antigens resemble that of adult or neonatal cells responsive to TD antigens? The answer is pertinent to determining the relative maturity of the B cells which can be tolerized or respond to TI or TD antigens. We report here the direct comparison of tolerogen sensitivity of adult and neonatal TD and TI responses by inducing tolerance in vitro with trinitophenyl human gamma globulin (TNP(17)HgG) and assaying unresponsiveness with TD and TI forms of the TNP determinant.

Animals↗
PubMed1977

Partial characterization of nervous system-specific cell surface antigen(s) NS-2.

Partial biochemical characterization of several neural tissue specific antigens isolated from a murine glioblastoma cell line was accomplished by means of radioiodination of intact cells followed by immunoprecipitation of the cell lysate with a rabbit serum specific for neural tissue antigens. Polyacrylamide gel electrophoresis of the immunoprecipitate in sodium dodecyl sulfate resolved the labeled antigens into several major components: two proteins (or glycoproteins) having apparent m.w.'s of 84,000 and 120,000 and lipid associated components which may be heterogeneous. The protein and lipid associated components apparently possess independent antigenicity because after chloroformmethanol extraction the protein components can be immunoprecipitated from the aqueous phase and the lipid associated component can be immunoprecipitated from the organic phase. Despite their independent antigenicity it is not known whether the components may be noncovalently associated on the cell surface. Although some of these antigens can be isolated from brain or glioma cells (a related tumor), non can be demonstrated in lymphoid tissues or C1300 neuroblastoma cells using identical methods. Therefore, these studies confirm our previous findings concerning the specificity of the anti-NS-2 antiserum by using cytotoxicity tests.

Animals↗
PubMed1977

Relationship between trinitrophenyl and H-2 antigens on trinitrophenyl-modified spleen cells. I. H-2 antigens on cells treated with trinitrobenzene sulfonic acid are derivatized.

Spleen cells were treated with TNBS in order to determine if cell surface H-2 antigens are derivatized with TNP. By labeling the cell membrane of the TNP-modified cells with 125I, followed by detergent lysis and immune precipitation with anti-TNP, it was determined that no H-2 antigenic activity remained in the supernatant. Further, by the use of an antibody-induced antigen redistribution assay it was found that previous exposure to TNP-modified cells to anti-TNP in the absence of complement rendered these cells resistant to lysis by anti-H-2 in the presence of complement. Together these data indicate that at the concentration of TNBS used for modification, H-2 antigens are derivatized with TNP. However, in addition to H-2, other proteins including immunoglobulin were also derivatized with TNP. Anti-TNP cytotoxic effector cells were blocked from their cytotoxic activity by anti-TNP antiserum. These data indicate that TNP directly couples to H-2 antigens on the cell surface of TNP-modified cells and that TNP is associated with the antigenic determinant that the cytotoxic T cell recognizes.

Animals↗
PubMed1977

Relationship between trinitrophenyl and H-2 antigens on trinitrophenyl-modified spleen cells. II. Correlation between derivatization of H-2 antigens with trinitrophenyl and the ability of trinitrophenyl-modified cells to react functionally to the CML assay.

Spleen cells were modified with varying concentrations of trinitrobenzene sulfonic acid and then assayed for both their ability to stimulate syngeneic spleen cells into displaying a cytotoxic effect against TNP-modified target cells and for the extent of TNP derivatization of H-2 antigens. It was found that there was a direct correlation between the extent of derivatization of H-2 antigens and the ability of such derivatized cells to act as stimulator cells in the TNP-CML assay. Thus, these data lend support to the altered self or interaction antigen hypothesis as the explanation for the H-2 gene restriction of syngeneic CML. Target cells were also modified with TNBS at varying concentrations to determine the optimal concentration required to permit lysis in the CML assay. The results of these experiments indicate that similar concentration ranges of TNBS are required to create antigenic determinants on the target cells as well as immunogenic determinants on the stimulator cells that can be recognized by cytotoxic T cells.

Animals↗
PubMed1977

B cell tolerance. I. Analysis of hapten-specific unresponsiveness induced in vitro in adult and neonatal murine spleen cell populations.

The cellular mechanisms and tolerogen dose requirements of hapten-specific unresponsiveness induced in vitro by using 2,4,6-trinitrophenyl human gamma-globulin (TNP17HgG) were analyzed in adult and neonatal murine splenocytes. Tolerance induction in both cell populations was found to be independent of non-B cell effects including BAtheta-positive cells, Ly 2.2-positive cells, adding or reducing the number of macrophages, and large excesses of HgG. The tolerance induced was specific and not "infectious", further excluding a role for suppressor T cells. Neonatal splenic B cells were rendered tolerant by doses of TNP17HgG 1000-fold less than those required to produce similar tolerance in splenic B cells from adults. These findings support the concept of functional clonal abortion as a mechanism for producing tolerance to self antigens.

Aging↗
PubMed1976

Beta 2-microglobulin is selectively associated with H-2 and TL alloantigens on murine lymphoid cells.

We have used a rabbit antiserum prepared against purified rat beta2-microglobulin to immunoprecipitate molecules from lysates of radioiodinated murine thymocytes and splenocytes. All the molecules that are reactive with this serum have subunits of 44,000 and 12,000 and can be identified as H-2 and TL antigens. Thus, the anti-beta2mu serum can deplete lysates of the majority of the TL and H-2 atigens which can be subsequently recognized by alloantisera. If TL and H-2 are precipitated from the lysates before the addition of anti-beta2mu, no beta2mu-reactive molecules remain. Our results indicate that Ia antigens cannot be depleted from the lysates with anti-beta2mu. The studies also suggest that TL and H-2 heavy chains can exist as both monomers and dimers. These observations are discussed with regard to previous studies concerning the native structure of H-2 and TL antigens.

Animals↗
PubMed1976

Differential susceptibility of neonatal and adult murine spleen cells to in vitro induction of B-cell tolerance.

The relative susceptibility of neonatal and adult murine splenocytes to induction of B-cell tolerance was studied in vitro. Adult cells required approximately 1,000-fold more trinitrophenyl-human gamma globulin to be rendered tolerant than did cells from 9- to 12-day-old neonates. The potential effects of suppressor T cells were excluded by pretreating the cultured B cells with anti-Thy-1 and C' and the helper T cells with anti-Ly-2.2 and C'. The possible role of cell surface immunoglobulin isotypes in contributing to this observed difference is discussed.

Aging↗
PubMed1976

Cell surface immunoglobulin. XVIII. Functional differences of B lymphocytes bearing different surface immunoglobulin isotypes.

Three populations of murine splenic B lymphocytes have been characterized previously (6, 7, 9) as those bearing only IgM, those bearing only IgD, and a population bearing both isotopes. These studies were designed to test the response of the IgM+ cells (IgM-only or IgM plus IgD) vs. the IgD-only cells to the B-cell mitogen, lipopolysaccharide. Results that after 1-4 days of culture, in the presence of mitogen, the IgM+ cells enlarge and elaborate an IgM polyclonal response. The IgD-only cells, in contrast, do not exhibit an IgM polyclonal response, but instead undergo blastogenesis and proliferation.

Animals↗
PubMed1976

Cell surface immunoglobulin. XV. The presence of IgM and an IgD-like molecule on the same cell in murine lymphoid tissue.

The present studies were designed to determine whether IgM and "IgD" are on the same cell in the mouse. Thus, radioiodinated murine lymphocytes were treated with anti-mu and complement to kill IgM-bearing cells. The dead cells were removed by gradient centrifugation. Results indicate that a portion of the IgD is removed by depleting IgM-bearing cells. Using cells from thoracic duct or lymph nodes but not spleen, it was evident that some of the double bearers are large lymphocytes.

Animals↗
PubMed1976

Structural studies on protein products of murine chromosome 17: partial amino acid sequence of an H-2Kb molecule.

By use of single internal radiolabels, 17 of the NH2-terminal 27 amino acids of the murine H-2Kb molecule have been assigned. When the amino acid sequence is compared to that of the murine H-2Kk molecule, there is a minimum of six amino acid differences in 19 positions. This high degree of structural diversity confirms, at the level of amino acid sequence, the known polymorphism of the murine H-2 complex. Significant primary str-ctural homology is evident when the murine H-2Kk and H-2Kb sequences are compared to the recently reported partial amino acid sequences of human transplantation antigens. There is modest homology with beta2-mictoglobulin and immunoglobulins, but the available sequence information is insufficient for a satisfactory evaluation of its significance.

Alleles↗
PubMed1976

The partial amino-acid sequence of an H-2K molecule.

Eighteen of the NH2-terminal 27 amino acids of a murine H-2K molecule have been assigned. The approach used was to label murine splenocytes with a single radioactive amino acid, isolate the H-2K molecule by specific immunoprecipitation, electrophorese the dissolved precipitate on sodium dodecyl sulfate polyacrylamide gels, and subject the isolated H-2K peak to amino-acid analysis and automated sequencing.

Amino Acid Sequence↗
PubMed1976

Cell surface immunoglobulin. XIX. Susceptibility of IgD and IgM on murine splenocytes to cleavage by papain.

The present studies were designed to determine the effect of papain upon IgM and IgD on the surface of murine splenocytes. By using radioiodinated cells, it was shown that IgD is more susceptible to cleavage by papain than IgM. The difference in susceptibility to papain of the two isotypes was not observed when cell lysates were employed, suggesting that attachment to the plasma membrane affects the accessibility of IgM to papain. The major site of attack of the enzyme on IgD appears to be in the hinge region. The possible biologic implications of such a cleavage are discussed.

Animals↗
PubMed1976

Relationship between beta2-microglobulin and cell-surface alloantigens of the mouse.

Molecular relationships between beta2m and other cell surface antigens (H-2, Tla, Ia, and Thy-1) were studied with the double immunofluorescence method. Cells were incubated with an antiserum against one antigen capped, and then tested with an antiserum against a second antigen. Capping of beta2m on thymocytes led to simultaneous capping of H-2 and Tla but not Thy-1 antigens; capping of H-2 and TIa (but not Thy-1) antigens resulted in capping of all beta2m detectable by the immunofluorescence method. Similarly, capping of beta2m on B or T lymphocytes resulted in capping of H-2 and vice versa. Ia antigens on B lymphocytes were not capped after the redistribution of beta2m. We conclude from these data that, in the cell membrane of thymocytes, virtually all the beta2m molecules are associated with H-2 and Tla, but not with Thy-1, and that on the cell surface of T or B lymphocytes, virtually all beta2m is associated with H-2 but not with Ia. We found no evidence of any significant free beta2m on either thymocytes or splenocytes.

Animals↗