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E M Shevach

Publications and source records attributed to E M Shevach.

At least 19 recordsLinked to original sources
PubMed1979

Macrophage-lymphocyte clusters in the immune response to soluble protein antigen in vitro. VII. Genetically restricted and nonrestricted physical interactions.

We have assessed the genetic restrictions on physical interactions between macrophages and central lymphocytes and between central and peripheral lymphocytes in antigen-specific macrophage-lymphocyte clusters with respect to I-region differences of inbred strains 2 and 13 guinea pigs. When using lymphocytes from guinea pigs immunized with DNP-OVA or DNP-GL in CFA, the antigen-specific interaction between central lymphocyte and macrophage requires that both cells be derived from animals syngeneic at the I-region of the major histocompatibility complex. In studies using antigens, the responses to which is under the control of MHC-linked Ir genes, macrophages from the responder, but not from the nonresponder parental strain support cluster formation with responder x nonresponder F1(2 X 13) T cells. In contrast, the physical interactions between central and peripheral T lymphocytes are not restricted by the I-region of the MHC and the peripheral lymphocyte need not be from an animal immune to the antigen used to drive macrophage central lymphocyte interactions.

Animals↗
PubMed1979

The activation of guinea pig T lymphocytes by anti-beta 2-microglobulin serum.

In order to study further the role of beta 2-m in the regulation of the immune response, we have examined the effects of a goat anti-guinea pig beta 2-m serum on a number of T lymphocyte functions in vitro. Anti-beta 2-m serum produced a marked inhibition of the response of peritoneal exudate T cells to antigen and mitogen stimulation. Surprisingly, a marked activation of lymph node T lymphocyte proliferation was observed in the absence of antigen or mitogen stimulation. This stimulatory effect of anti-beta 2-m serum was shown to be specific for beta 2-m and required the presence of macrophages. The T cell proliferative response induced by anti-beta 2-m could not be blocked by antisera to the antigens of the guinea pig MHC. These studies suggest that beta2-m may play some critical role in the immune response at the level of T cell activation.

Animals↗
PubMed1979

Analysis of guinea pig membrane proteins recognized by heterologous antilymphocyte sera. Specific recognition of Ia alloantigens.

Heterologous antilymphocytes sera (ALS) produced in several species against a variety of guinea pig lymphocytes populations were studied by immunoprecipitation experiments and polyacrylamide gel electrophoretic analyses to characterize the membrane proteins recognized by these antisera. Although a number of different proteins were recognized by these sera, high-titered antibodies against guinea pig Ia antigens could be demonstrated in all ALS, including those produced against thymocytes. Furthermore, selective absorptions and sequential precipitation experiments revealed significant levels of xenoantibodies that recognized specific Ia alloantigenic determinants. The potential significance of antibodies against Ia antigens in heterologous antilymphocyte and antithymocyte sera is discussed.

Absorption↗
PubMed1979

Specific absorption of T lymphocytes committed to soluble protein antigens by incubation on antigen-pulsed macrophage monolayers.

Monolayers of macrophages (Mphi) pulsed with antigen were used as immunosorbents for T lymphocytes from guinea pigs primed to soluble protein antigens. T lymphocytes were cultured on the Mphi monolayers for 4 hr, then aspirated and reincubated on a fresh monolayer pulsed with the same antigen for a second and a third step. T lymphocytes so treated were selectively deprived of cells responding in assay for antigen-dependent proliferation against the antigen used for pulsing the absorbing monolayer, but maintained their response to other antigens. The lymphocytes adhering to the Mphi of the absorbing monolayer were capable of giving a full response to the antigen used for pulsing the Mphi of the monolyers. The proliferative response of F1 T lymphocytes to antigen in association with Mphi of either parental strain could be absorbed leaving the response to antigen in association with Mphi of the other parental strain. The absorption of the proliferative response was not inhibited by addition of excess soluble antigen to the medium of the absorption culture. Our results indicate that specific guinea pig T lymphocytes responding by proliferation to soluble protein antigens recognize and bind specifically to a complex of Ia antigen and protein antigen at the surface of the Mphi.

Absorption↗
PubMed1979

Role of nominal antigen and Ia antigen in the binding of antigen-specific T lymphocytes to macrophages.

We have previously demonstrated that when primed T lymphocytes were repeatedly incubated on monolayers of antigen-pulsed macrophages (M phi), the cells that failed to adhere to the monolayer demonstrated a marked depletion of their proliferative response that was specific both for the antigen used for pulsing the M phi and for Ia determinants on the M phi. In order to further analyze the contribution of the nominal antigen and Ia antigens to the physical binding of T lymphocytes to M phi, we have attempted to block the absorption of T lymphocytes to M phi with a large excess of soluble antigen and with anti-Ia sera. Our results demonstrate that anti-Ia sera inhibit but that soluble antigen augments the binding of specific T lymphocytes to M phi. The implications of these findings for "dual recognition" and "linked recognition" models of T lymphocyte receptors are discussed.

Animals↗
PubMed1978

The histocompatibility restrictions on macrophage T-helper cell interaction determine the histocompatibility restrictions on T-helper cell B-cell interaction.

To study the histocompatibility restriction between macrophages and helper T cells, carrier primed guinea pig T cells were positively selected in vitro with antigenpulsed macrophages for 7 days and the selected T cells were then mixed with hapten-primed B cells and stimulated with antigen in a modified Mishell-Dutton system. Helper T cells could only be selected with syngeneic, but not allogeneic, antigen-pulsed macrophages and would then collaborate only with syngeneic, but not allogeneic, hapten-primed spleen cells. When F1 T cells were selected with antigen-pulsed parental macrophages they would only collaborate with B cells of the same parental strain as the macrophages used in the selection culture. These results are strongly in support of the view that the primed T cell is activated by carrier determinants of the nominal antigen in association with Ia antigens on macrophages and the helper T cell, in turn, activates B cells which bear the same Ia antigens and determinants of the nominal antigen bound to immunoglobulin receptors on their surface. In addition, in experiments with antigens the response to which is controlled by I-linked genes, we demonstrated that primed (responder X nonresponder)F1 T cells would only collaborate with B cells of the responder parent. The defect appeared to be at the level of the B cell in that the addition to the cultures of antigen-presenting cells of the responder type did not restore the ability of F1 T cells to collaborate with non-responder B cells.

Animals↗
PubMed1978

Analogous functions of macrophages and Langerhans cells in the initiation in the immune response.

Langerhans cells constitute a minor cell population within the mammalian epidermis. This paper defines these cells immunologically and functionally and supports the concept that Langerhans cells are closely related to cells from the monocyte-macrophage-histiocyte series. Both cell types bear surface receptors for Fc-IgG and C3 and express surface glycoproteins, termed Ia antigens, encoded for by immune-response genes (Ir genes) of the major histocompatibility complex of the species. The expression of Ia antigens by Langerhans cells and macrophages is intimately associated with important functions of both cell types, including the capacity to present immunologically relevant antigen to the T lymphocyte and to cause proliferation to allogeneic T lymphocytes in mixed leukocyte reactions.

Animals↗
PubMed1978

Nature of the antigenic complex recognized by T lymphocytes. V. Genetic predisposition of independent F1 T cell subpopulations responsive to antigen-pulsed parental macrophages.

Nonimmune (2 x 13)F1 guinea pig T lymphocytes initially stimulated with trinitrophenyl- (TNP) modified macrophages from one parental strain and then treated with bromodeoxyuridrine (BUdR) and light are unable to be primed subsequently with TNP-modified macrophages of the same parental strain. In contrast, these BUdR and light treated F1 T cells can be primed with TNP-modified macrophages of the other parental strain. These results demonstrate that in a nonimmune F1 animal two T cell subpopulations exist before priming that are genetically predisposed to respond to antigen associated with macrophages derived from one or the other parent.

Animals↗
PubMed1978

The expression of Ia antigens on immunocompetent cells in the guinea pig. III. Functional selection of Ia-negative T cells by in vitro culture.

In the present study we examined the expression of I-region-associated (Ia) antigens by guinea pig T lymphocytes stimulated in vitro with antigen-pulsed macrophages. Treatment of lymph node (LNL) or peritoneal exudate (PEL) T cells taken directly from immune animals with anti-Ia serum and complement (C) dramatically reduced their proliferative response to antigen-pulsed macrophages when determined on the 4th day of culture. In contrast, the response of immune T cells that had been selected by culture for a week with antigen-pulsed macrophages and restimulated in a second culture was not affected by anti-Ia and C treatment. This same result occurred with selected LNL or PEL that were initially treated before the selection culture with either normal serum or anti-Ia serum and C. LNL became resistant to anti-Ia serum and C treatment by 3 days of culture whereas antigen-specific PEL were still sensitive at that time. These results indicate that in an immune animal two antigen-specific T cell subpopulations are generated based on their sensitivity to anti-Ia serum and C treatment, but that only the resistant population is selected by in vitro culture. In addition, we demonstrated that the Ig-negative T cell population can only be activated by histocompatible antigen-pulsed macrophages.

Animals↗
PubMed1978

Guinea pig homologues of TL and QA-2 antigens.

The H-2, thymus-leukemia (TL), and Qa-2 antigens of mice are encoded by closely linked genes on murine chromosome 17, and have structural similiarity in that each antigen is borne on a approximately 44,000 dalton molecule associated with beta2 microglobulin (beta2mu). The extensive homology of major histocompatibility complex (MHC) products that exists for the mouse and guinea pig suggested that a similar homology might exist for products of genetic regions closely linked to the MHC. By taking advantage of the selective association of beta2mu with H-2, Qa-2, and TL antigens, and by using the technique of sequential immunoprecipitation, we demonstrated two previously undescribed guinea pig molecules reactive with anti-guinea pig beta2mu. The first molecule was composed of a 36,000 dalton glycoprotein associated with beta2mu and was found on guinea pig thymocytes, but not lymphocytes. The second molecule was composed of a 40,000 dalton glycoprotein associated with beta2mu, and was found on both guinea pig thymocytes and lymphocytes. By structure, chemical composition, association with beta2mu, and tissue distribution, the first molecule is an attractive candidate for the guinea pig homologue of TL antigen, whereas the second fits the criteria for the guinea pig homologue of Qa-2 antigen.

Animals↗