Genetic restrictions for the induction of suppressor T cells by hapten-modified lymphoid cells in tolerance to 1-fluoro-2,4-dinitrobenzene contact sensitivity. Role of the H-2D region of the major histocompatibility complex.

Abstract

Gene products of the major histocompatibility complex (MHC) 1 are associated with various effector and cooperative functions of immunocompetent lymphoid cells (1). The I region of the MHC is associated with the induction of helper T cells (2), the proliferative response of T cells to allogeneic cells (3) and to antigen-pulsed macrophages (4), cooperation of T helper cells with B cells (5), and the adoptive transfer of delayed-type hypersensitivity (DTH) to fowl gamma globulin (6). Gene products of the H-2K and/or H-2D regions of the MHC are associated with T-cell-mediated cytolysis of virus-infected (7) or hapten-modified (8) target cells, and the~transfer of DTH to murine lymphocytic choriomeningitis virus (9).We have recently been studying the induction and mechanisms of haptenspecific T-cell tolerance to 1-fluoro-2,4-dinitrobenzene (DNFB) contact sensitivity by using dinitrophenyl (DNP)-modified lymphoid cells (DNP-LC) as tolerogens (10). Tolerance induced by DNP-LC has been functionally separated into two mechanisms-clone inhibition and the participation of suppressor T cells (Ts) (11). We have also reported that the induction of Ts by DNP-syngeneic LC (syninduced Ts) (12) as well as the expression of Ts induced by DNP-allogeneic LC (alloinduced Ts) (13) is genetically restricted by MHC gene products. In the present report, we have investigated these genetic restrictions by using congenic resistant mouse strains. The results indicate that both syninduced and aUoinduced Ts are activated by hapten-modified determinants coded for by the H-2D region of the MHC. Furthermore, the results show that alloinduced Ts are

MHC imbalance and metastatic spread in Lewis lung carcinoma clones

“…This seems compatible with recent demonstrations that these two class I molecules manifest different immune functions. The results of Wernet and Lilly (1975), Miller et al (1978), Hasek and Chutna (1979) and others support the assumption that the display of H-2D-region-associated antigens may favor induction of suppressor cells as distinct from H-2K, which manifests an immunogenic effect. Schmidt and Festenstein (1982) have recently shown that clones of AKR leukemias which had lost the H-2Kk expression did not act as inducers of Gross M~LV/H-2~-specific cytotoxic T lymphocytes.…”

“…These modulations can be based on quantitative alterations (Haywood and McKhann, 1971; Ting and Herberman, 1971; De Baetselier et al, 1983), specific to one gene product (De Baetselier et al, 1980;Schmidt and Festenstein, 1982) (Katzav, 1983). Previous studies indicated that gene products of the K and D ends might manifest different immunogenic properties (Wernet and Lilly, 1975;Miller et al, 1978;Hasek and Chutna, 1979). Furthermore Schmidt and Festenstein (1982) demonstrated that the absence from tumor cells of K-end expression reduces the immunogenic effect of tumor cells and their susceptibility to syngeneic CTL.…”

“…Metastatic and nonmetastatic clones of T10 sarcoma were found in our laboratory to express different alloantigens (Katzav et al, 1981) and changes in the metastatic phenotype were associated with altered MHC expression (Katzav, 1983). Previous studies indicated that gene products of the K and D ends might manifest different immunogenic properties (Wernet and Lilly, 1975;Miller et al, 1978;Hasek and Chutna, 1979). Furthermore Schmidt and Festenstein (1982) demonstrated that the absence from tumor cells of K-end expression reduces the immunogenic effect of tumor cells and their susceptibility to syngeneic CTL.…”

Cell Surface Expression of I‐A Products Is Required for Contact Sensitivity Induction by Trinitrophenyl‐Coupled Epidermal Cells

“…Gene products of the H-2K and/or H-2D regions of the MHC are associated with T cell-mediated cytolysis of virus-infected or hapten-modified target cells (22,29), and the activation of suppressor T cells (Ts) by hapten-conjugated lymphoid cells (14,15). Gene products of the I region (Ia antigens) are associated with the induction of helper T cells (TH) (6), the proliferative response of T cells to antigenpulsed macrophages .…”

Regulated expression of a murine class I gene in transgenic mice.

“…A previous observation that elevated expression of the D gene is correlated with resistance to leukemia (12,13) can now be directly tested to determine whether any causal relationship exists. The suggestion that the D antigen may exhibit suppressive effects on the immune response of the host (6,14,26) and hence allow the escape of tumor cells from immunosurveillance can also be ascertained with these transgenic mice. If the nonexpression of class I genes is responsible for the malignant and metastatic phenotypes of tumor cells (8,22,24), it will be of utmost importance to determine whether the expression of the transgenic class I gene can be suppressed concommitently with the endogenous class I genes upon transformation by human adenovirus type 12 (19 …”