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C G Fathman

Publications and source records attributed to C G Fathman.

13 recordsLinked to original sources
PubMed1979

Crossreactive mixed lymphocyte reaction determinants recognized by cloned alloreactive T cells.

We have isolated clones of alloreactive T cells by soft agar cloning of primed responder cells contained in serially restimulated, mixed lymphocyte cultures. These clones recognize unique mixed lymphocyte reaction (MLR) stimulating determinants present on (C57B/6 X A/J)F1 (B6A) spleen cells. By assaying the reactivity patterns of these clones on a panel of stimulator cells, we have identified at least three separate "specificities" of alloreactive T cell clones. Several clones exhibiting one of these three reactivity patterns have been isolated on many occasions from different experiments. Using such clones of alloreactive T cells, we have identified and are attempting to define crossreactive MLR stimulating determinants exhibited by a panel of stimulator cells. Recognition by certain clones of a shared MLR determinant(s) on B6A and DBA/2 and of the lack of this determinant(s) on B6 stimulator cells questions current concepts concerning the nature of MLR stimulating determinants and T cell recognition of alloantigens.

Animals↗
PubMed1979

Non-H-2 linked control of low versus high responses of antigen-induced lymph node cell proliferation: possible role for antigen-presenting cells.

Quantitative differences in the magnitude of antigen-induced proliferative responses of sensitized lymph node cells between low (C3H/Anf or C3H/Cr) and high (C3H/Hej or CBA/j) responder H-2k mice have been observed 1 to 2 weeks after in vivo sensitization with antigen (OVA, PPD, and GAT). We have shown that antigen presentation is less effective in the sensitized lymph node cell populations from low responder mice compared with those from high responder mice, suggesting that the number and/or functional status of antigen-presenting cells in the regional lymph nodes may be a key factor in determining the magnitude of antigen-induced proliferative responses. These data are consistent with the hypothesis that cell traffic after sensitization plays an important role in determining the immune responsiveness of lymph nodes.

Animals↗
PubMed1978

In vitro secondary MLR. III: Hybrid histocompatibility determinants.

With cells obtained from long-term mixed lymphocyte culture (MLC) we have have demonstrated hybrid histocompatibility determinants that are recognized as mixed lymphocyte reaction (MLR)-stimulating determinants. Hybrid determinants can also be detected (1) in an in vitro assay for effector cells that measure inhibition of immunoglobulin secretion by LPS-blasts, and (2) in DTH-like responses of in vitro-primed cells injected into "B" mice and challenged in vivo with stimulator cells. The possible implications of these findings for the physiologic function of MLR determinants are discussed.

Animals↗
PubMed1977

Genetic control of the immune response to nuclease. V. Genetic linkage and strain distribution of anti-nuclease idiotypes.

Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes.

Animals↗
PubMed1977

In vitro secondary mixed leukocyte reaction (MLR). II. Interaction MLR determinants expressed by F1 cells.

T cells from strain A primed in vitro to (C57BL/6 x A/JF1 [(B6 x A)F1] cells respond better to restimulation by (B6 x A)F1 than by B6 or a 1:1 mixture of A and B6 cells. The increase in the response to F1 cells is specific and due to MLR determinants present on (B6 x A)F1 cells but not on either of the parental cell types. (B6 x A)F1 cells express more than one F1-specific MLR determinant, and this expression is dependent upon products of alleles of at least two loci within the major histocompatibility complex (MHC). Responsiveness to these F1-MLR determinants is apparently controlled by more than one locus within the MHC.

Animals↗
PubMed1977

H-2 gene complementation in cytotoxic T cell responses of female against male cells.

H-2 gene-dependent nonresponsiveness and responsiveness to H-2-matched male cells can be observed in cytotoxic assays in several mouse strains. H-2 genes of several low responder strains can complement each other in cis or trans position to produce high responders. One of the H-2 gene products functions at the level of antigen-presenting cells (stimulators, targets), the other must be expressed in the responding T cell population.

Animals↗
PubMed1977

T cells which proliferate in response to concanavalin A include cells which proliferate in mixed leucocyte reactions.

Selection in long-term culture of alloreactive T cells, by successive in vitro restimulation with semi-allogeneic cells, results in primed responder cell populations which maintain full proliferative reactivity to allogeneic cells as well as to the T cell mitogens concanavalin A (Con A) and phytohemagglutinin (PHA) but are depleted of cells which can effect target cell destruction in either a specific or nonspecific manner. Con A-induced T cell blasts (selected by velocity sedimentation) can revert to small resting lymphocytes in the presence of inert "filler" cells. Con A blasts which have reverted, readily proliferate in response to Con A or allogeneic stimulator cells but are largely depleted of effector killer cells and PHA-responsive cells.

Animals↗
PubMed1977

In vitro secondary MLR. I. Kinetics of proliferation and specificity of in vitro primed responder cells.

We have examined the kinetics and specificity of secondary in vitro mixed lymphocyte reactions (MLR). With limited numbers of primed responder cells (PRC) in the presence of "excess antigen" it was possible to obtain proliferative responses that were proportional to the number of PRC initially placed in culture. The responding cells, after an initial lag period, seem to grow exponentially until day 3 of culture. The responses of PRC (with the strain combinations and culture conditions described in this report) seemed to be directed toward stimulator cell determinants whose expression was determined by genes in the I region of the MHC. In one case, the relevant incompatibilities could be further restricted to the I-A region. Although PRC responded best to stimulator cells sharing the I region with the priming stimulator cell, apparent cross-reactivity could be observed by restimulating PRC with stimulator cells that did not carry the MHC haplotype of the priming stimulator cell. The rate of proliferation (measured as 3H-thymidine incorporation) in these apparent cross-reactions was reproducible and comparable to the rate observed in response to the priming stimulator cell. It was possible, therefore, to estimate the proportion of PRC that reacted in the presence of third party stimulator cells compared to the response of these PRC to the priming stimulator cells. We have estimated that the response of A (B6) PRC against H-2d and H-2s haplotype stimulator cells is about half of the response of these PRC to H-2b, the priming stimulator cell.

Animals↗
PubMed1976

Inhibition of stimulation in murine mixed lymphocyte cultures with an alloantiserum directed against a shared Ia determinant.

Pools of high titered alloantisera were raised by immunizing (B10.A/SgSn X A/WySn)F1 mice with C57BL/10Sn(B10) spleen cells. This serum (F1 anti-B10), when added to one-way mixed lymphocyte cultures (MLC), inhibited stimulation of B10.A splenic responders by both B10 and B10.D2/nSn irradiated, splenic stimulators. The B10 stimulation was suppressed approximately 85% whereas the mean suppression of B10.D2 stimulation was approximately 60%. In the ofrmer case, the serum contained antibodies reactive with multiple major histocompatibility complex determinants on the stimulator cells. In the latter case, the cytoxic reactivity of the serum was directed principally against an I region-associated determinant Ia.8) shared by B10 and B10.D2 and coded for by a gene(s) in the I-A subregion. The magnitude of the suppression of the response to B10.D2 cells (60%) was similar to the reduction in stimulation observed when the Ia.8 difference was eliminated genetically by using (B10 X B10.A)F1 responder cells against irradiated B10.D2 stimulators. Ihhibition of MLC by this antiserum was a function of reactivity with stimulator and not responder cells. Although some pools of F1 anti-B10 antiserum produced partial inhibition of the responder cell in a B10.D2 vs B10.Ax MLC combination, the results were inconsistent and not correlated with the anti-Ia.8 cytotoxicity titers. In addition, an F1 anti-B10 antiserum pool, which consistently failed to inhibit the responder cell, nevertheless inhibited both irradiated B10.D2 and (B10.A X B10.D2)F1 cells from stimulating B10.A responder cells. However, this same antiserum did not inhibit stimulation of B10.D2 responder cells by the (B10.A X B10.D2)F1 stimulators. Thus, the binding of antibodies to the non-stimulating antigens on the F1 stimulator cell did not interfere with the capacity of the appropriate stimulating antigens to cause stimulation. All of these results are consistent with the hypothesis that Ia allo-antigens are the major stimulating determinants of I region-associated MLC reactions.

Animals↗
PubMed1976

Genetic control of the immune response to nuclease. II. Detection of idiotypic determinants by the inhibition of antibody-mediated nuclease inactivation.

The humoral response of mice to staphylococcal nuclease has previously been shown to be controlled genetically by H-2-linked Ir gene(s). In order to examine the possible contributions of variable region immunoglobulin genes to this genetic control, we have developed a system for the detection of idiotypic determinants on anti-nuclease immunoglobulin molecules. Antisera to nuclease were raised in two high responder strains, A/J and SJL. The corresponding antibodies were purified by affinity chromotography on Sepharose-nuclease columns, and were used to immunize groups of Lewis rats. An assay system was developed to assess the inhibition of antibody-mediated inactivation of nuclease activity by the rat antisera thus produced. Despite the presence of many species-specific anti-mouse immunoglobulin antibodies in these sera, inhibition of antibody-mediated enzyme inactivation was found to be specific for anti-nuclease antibodies of the immunizing strain. The inhibition could not be removed by extensive absorption with normal serum proteins from the antibody-producing strain, and was shown to require antibodies directed toward binding sites of the anti-nuclease antibodies. This inhibition thus defines idiotypic determinants of anti-nuclease antibodies.

Absorption↗