scholarly journals Regulation of immune responses by I-J gene products. II. Presence of Both I-Jb and I-Jk suppressor factors in (nonsuppressor x nonsuppressor) F1 mice.

1982 ◽  
Vol 155 (4) ◽  
pp. 955-967 ◽  
Author(s):  
H Y Lei ◽  
M E Dorf ◽  
C Waltenbaugh
Keyword(s):  
Immune Responses ◽  
Suppressor Cells ◽  
Antigenic Determinants ◽  
Gene Products ◽  
Suppressor Factor ◽  
F1 Hybrid ◽  
Gene Complementation ◽  
Specific Suppression ◽  
Hybrid Mice ◽  
Immune Suppressor

Antigen-specific suppression to poly(Glu50-Tyr50) (GT) is under the control of two complementary immune suppressor (Is) genes located in the major histocompatibility (H-2) complex of the mouse. Suppressor strains of mice produce both suppressor T (Ts) cells and Ts-derived suppressor factors (TsF) that bear antigenic determinants of the I-J subregion of the H-2 complex. Nonsuppressor strains of mice, on the other hand, are not suppressed by GT preimmunization. These nonsuppressor mice, however, can be classified according to those that lack the ability to make GT-specific T cell-derived suppressor factor (GT-TsF) after GT injection (i.e., H-2a, I-Jk mice) and those that lack the ability to be suppressed by the appropriate GT-TsF (i.e., H-2b,g2, I-Jb mice). In the present study, we demonstrate that (H-2a x H-2b,g2)F1 hybrid mice produce distinct GT-specific suppressor factors of both parental I-J haplotypes. Moreover, only the I-Jb-bearing GT-TsF derived from these F1 hybrid mice is able to induce second-order suppressor cells (Ts2). This is consistent with the observation that injection of GT-TsF1 derived from C57BL/6 (I-Jb) mice into A/J (I-Jk) mice leads to the production of an antigen-specific I-Jk GT-TsF2. Our results suggest that Is gene complementation occurs through a different cellular mechanism that was previously observed for Ir gene complementation. Further, we show that complementing (non-suppressor X nonsuppressor)F1 hybrid mice produce an I-Jb (and not an I-Jk) GT-TsF1 and an I-Jk (not an I-Jb) GT-TsF2, thus suggesting a heterogeneity of Ia loci within the I-J subregion. Data presented in the present study suggest that there may be even more heterogeneity within the I-J subregion than has has been heretofore reported with regard to I-J expression on Ts.

scholarly journals Regulation of immune responses by I-J gene products. I. Production and characterization of anti-I-J monoclonal antibodies.

1981 ◽  
Vol 154 (5) ◽  
pp. 1570-1583 ◽  
Author(s):  
C Waltenbaugh
Keyword(s):  
T Cells ◽  
Monoclonal Antibodies ◽  
Immune Responses ◽  
Biochemical Characterization ◽  
Antigenic Determinants ◽  
Functional Screening ◽  
Gene Products ◽  
Suppressor Factor

Using a novel, two-step functional screening procedure, we have isolated hybridoma B cell lines secreting monoclonal antibodies directed against gene products of the I-Jb and I-Jk subregions of the mouse H-2 complex. These monoclonal antibodies act in vitro by allowing nonresponder spleen cells to respond to normally suppressive quantities of poly(Glu50Tyr50) (GT) (WF8 series of anti-I-Jk monoclonal antibodies) or to suboptimal concentration of poly(Glu60Ala30Tyr10) (WF9 series of anti-I-Jb monoclonal antibodies). Some of the culture supernates that show augmenting activity bind GT-specific T cell-derived suppressor factor (GT-TsF), indicating that some monoclonal antiantibodies display a nonspecific enhancing effect, or, more likely, that anti-I-J monoclonal antibodies have been produced against I-J determinants not found on TsF. It is this last possibility that is most intriguing and that might serve as a means for exploring the heterogeneity of the I-J subregion. It is also possible that some of our monoclonal anti-I-J antibodies might detect antigenic determinants selectively expressed on suppressor T cells, helper T cells, and/or macrophages. In addition, we have demonstrated that monoclonal anti-I-J antibodies should be useful in the biochemical characterization and purification of a monoclonal GT-TsF. These haplotype-specific anti-I-J monoclonal antibodies should prove to be powerful tools for future studies exploring the role of I-J gene products in the regulation of specific immune responses.

Regulation of Immune Responses in SJL and F1 Hybrid Mice by γ-Irradiated Syngeneic Lymphoma Cells23

1984 ◽  
Vol 72 (1) ◽  
pp. 125-132 ◽  
Author(s):  
Irene R. Katz ◽  
Fumihiko Nagase ◽  
Melvin K. Bell ◽  
Nicholas M. Ponzio ◽  
G. Jeanette Thorbecke
Keyword(s):  
Immune Responses ◽  
F1 Hybrid ◽  
Hybrid Mice

scholarly journals Mechanisms of regulation of cell-mediated immunity. III. The characterization of azobenzenearsonate-specific suppressor T-cell-derived-suppressor factors.

1979 ◽  
Vol 149 (5) ◽  
pp. 1069-1083 ◽  
Author(s):  
M I Greene ◽  
B A Bach ◽  
B Benacerraf
Keyword(s):  
T Cell ◽  
Suppressor Cells ◽  
Binding Specificity ◽  
Delayed Type Hypersensitivity ◽  
Antigen Binding ◽  
Gene Products ◽  
Suppressive Activity ◽  
Spleen Cells ◽  
Suppressor Factor ◽  
Suppressor T Cell

Delayed type hypersensitivity to the hapten azobenzenearsonate (ABA) can be induced and suppressed by the administration of hapten-coupled syngeneic spleen cells by the appropriate route. Suppressor T cells stimulated by the intravenous administration of ABA-coupled spleen cells have been shown to produce a discrete subcellular factor(s) which is capable of suppressing delayed type hypersensitivity to azobenzenearsonate in the mouse. Such suppressor factors may be produced by the mechanical disruption of suppressor cells or by placing such suppressor cells in culture for 24 h. The suppressor factor(s) (SF) derived from ABA-specific suppressor cells exhibit biological specificity for the suppression of ABA delayed type hypersensitivity (DTH), but not trinitro-phenyl DTH, as well as the capacity to bind to ABA immunoadsorbents. Passage of suppressor factor(s) over reverse immunoadsorbents utilizing a rabbit anti-mouse F(ab')2 antiserum demonstrated that the antigen-specific T-cell derived SF does not bear conventional immunoglobulin markers. The suppressor factor(s) are not immunoglobulin molecules was further demonstrated by the inability of anti-ABA antibodies to suppress ABA DTH. Gel filtration of ABA suppressor factor(s) showed that the majority of the suppressive activity was present in a fraction with molecular weight ranging between 6.8 x 10(4) and 3.3 x 10(4) daltons. We also analyzed for the presence of determinants encoded by the H-2 major histocompatibility complex (MHC) and found that immunoadsorbents prepared utilizing antisera capable of interacting with gene products of the whole or selected gene regions of H-2 MHC, i.e., B10.D2 anti-B10.A and B10 anti-B10.A immunoadsorbents, retained the suppressive activity of ABA-SF. Elution of such columns with glycine HCl buffers (pH 2.8) permitted recovery of specific suppressive activity. Taken collectively such data supports the notion that suppressor T-cell-derived ABA suppressor factors have antigen-binding specificity as well as determinants controlled by the K end of the H-2 MHC. The distribution of strains capable of making SF has also been analyzed. The relationship of the antigen-binding specificity to VH gene products is discussed in this and the companion paper.

Suppressor cells and immunodeficiency in (NZB × NZW)F1 hybrid mice

1979 ◽  
Vol 9 (6) ◽  
pp. 440-446 ◽  
Author(s):  
Joseph P. Michalski ◽  
Candace C. McCombs ◽  
Norman Talal
Keyword(s):  
Suppressor Cells ◽  
F1 Hybrid ◽  
Hybrid Mice

scholarly journals Regulatory mechanisms in cell-mediated immune responses. VIII. Differential expression of I-region determinants by suppressor cells and their targets in suppression of mixed leukocyte reactions.

1979 ◽  
Vol 150 (5) ◽  
pp. 1108-1121 ◽  
Author(s):  
S S Rich ◽  
C S David
Keyword(s):  
T Cells ◽  
Phenotypic Expression ◽  
Suppressor Cells ◽  
Target Cells ◽  
Gene Products ◽  
Suppressor Activity ◽  
Suppressor Factor ◽  
Cytotoxic Studies ◽  
Marked Suppression

The phenotypic expression of I-region determinants on cells producing and responding to MLR suppressor factor (MLR-TsF) was established in these studies. Alloantigen-activated MLR suppressor T cells (MLR-Ts), which produce MLR-TsF bearing gene products of the I-C subregion, were exposed to anti-I subregion sera and complement (C) before in vitro culture for MLR-TsF production. Suppressor activity was prevented by removal of cells bearing I-C determinants, whereas elimination of cells expressing I-A/B determinants had no effect. Interestingly, cytotoxic elimination of cells displaying I-J determinants also prevented MLR-TsF production. Admixture of anti-I-J and I-C antiserum-treated cells for MLR-TsF production failed to reconstitute suppressor activity, indicating that I-C and I-J gene products are expressed on a single population of cells critical to MLR suppression, rather than on distinct interacting subpopulations. Anti-I-C serum activity specific for I-C+ MLR-Ts was removed by adsorption with nylon wool-nonadherent splenic T cells and concanavalin A-activated thymocytes; adsorption with splenic B cells from anti-Thy-1,2 serum and C-treated spleen failed to remove relevant anti-I-C activity. These data suggest that regulatory I-C molecules, like I-J molecules, are preferentially expressed on T lymphocytes. Expression of I-C, or other I-region molecules on responder cell targets of MLR-TsF activity was also investigated. Responder cells were pretreated with anti-I subregion-specific sera in blocking or complement-dependent cytotoxic protocols before addition to MLR with MLR-TsF. Neither blocking nor the cytotoxic removal of cells bearing I-C or other I-region determinants from MLR responder populations interfered with MLR-TsF suppression. Because it has previously been demonstrated that MLR-TsF interacts optimally with activated, I-C syngeneic target cells, blocking and cytotoxic studies with anti-I subregion sera were also performed with responder cells activated by 24 h culture in MLR in the absence of MLR-TsF. Brief MLR-TsF pulse after antiserum treatment generated marked suppression regardless of blocking or absence of cells bearing serologically detected I-region determinants. I-C restricted suppression may thus be mediated not by interaction with I-C-bearing cells, but by target cells which exist in requisite association with populations of I-C+ cells.

scholarly journals Regulation of immune responses by I-J gene products. VI. Recognition of I-E molecules by I-J-bearing suppressor factors.

1986 ◽  
Vol 163 (4) ◽  
pp. 797-811 ◽  
Author(s):  
C Waltenbaugh ◽  
L Sun ◽  
H Y Lei
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Inbred Mouse ◽  
Mouse Strains ◽  
Gene Products ◽  
Suppressor T Cells ◽  
Primary Target ◽  
Suppressor Factor ◽  
B Lymphoma Cells

Poly(Glu50Tyr50) (GT) is not immunogenic in most inbred mouse strains. GT injection produces an I-J--bearing, GT-specific T-cell--derived suppressor factor (GT-TsF1) in H-2b,d,k haplotype mice. GT-TsF1 generates second-order suppressor T cells (Ts2) in H-2a,d,k haplotype mice. Here, we show that in order for GT-TsF1 to act, the recipient strain must express I-E molecules. This suggests that T cells are not the primary target of GT-TsF1. GT-TsF1 can be presented by Ia+ A20-2J B lymphoma cells. GT-TsF1 presentation is blocked by anti-I-E, but not by anti--I-A, mAb, whereas GAT presentation is blocked by anti-I-A, but not by anti--I-E, mAbs. These data suggest that I-J recognizes (or is recognized by) I-E. The existence and role of I-J molecules in immune regulation are discussed in light of these data.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. VII. Presence of I-C subregion determinants on mixed leukocyte reaction suppressor factor.

1979 ◽  
Vol 149 (1) ◽  
pp. 114-126 ◽  
Author(s):  
S S Rich ◽  
C S David ◽  
R R Rich
Keyword(s):  
Major Histocompatibility Complex ◽  
T Cell ◽  
Immune Responses ◽  
Regulatory Mechanisms ◽  
Gene Products ◽  
Mixed Leukocyte Reaction ◽  
Suppressor Activity ◽  
Suppressor Factor ◽  
Histocompatibility Complex ◽  
D Region

The presence of H-2 gene products on mixed leukocyte reaction (MLR) supressor factor was investigated by passage of MLR-suppressor factor (SF) over solid immunoadsorbents prepared with various anti-H-2 subregion sera. Antisera with specificity for all or certain I subregion determinants removed or significantly reduced suppressor activity; adsorption was not consistent with K or D region specificity. The single I subregion specificity common to all adsorbing preparations was I-C. Serologic differentiation of I-C products of k and d haplotypes expressed on MLR-SF was established with antisera prepared in I-Cd/I-Ck disparate strain combinations. These sera define allelic T cell restricted Lad determinants encoded by I-C genes. MLR-SF prepared from (BALB/c X CBA)F1 mice and exposed to the I-Cd and I-Ck specific adsorbents demonstrated d and k haplotype specific adsorption respectively. F1 suppressor activity adsorbed on an anti-I-Cd column was eluted by glycine-HCl buffer and suppressed only BALB/c (H-2d) responses. B10.A suppressor activity was removed by anti-I-Cd sera, but was unaffected by anti-I-Ck sera, indicating that B10.A suppressor activity is encoded by an I-C subregion derived from the d haplotype. Antisera with anti-I-Jk specificity did not remove suppressor activity of various H-2k factors. Finally, adsorption with antisera directed against H-2-associated determinants of the allogeneic cell used to stimulate suppressor factor generation demonstrated that sensitizing alloantigens are not components of MLR suppressor factor. Thus among the major histocompatibility complex (MHC)-controlled suppressor factors, MLR suppressor factor is uniquely determined by the I-C subregion.

scholarly journals Regulatory mechanisms in cell-mediated immune responses. VI. Interaction of H-2 and non-H-2 genes in elaboration of mixed leukocyte reaction suppressor factor

1977 ◽  
Vol 146 (5) ◽  
pp. 1221-1233 ◽  
Author(s):  
SS Rich ◽  
FM Orson ◽  
RR Rich
Keyword(s):  
Parental Strain ◽  
Cell Activity ◽  
Suppressor Cells ◽  
Suppressor Cell ◽  
Spleen Cells ◽  
Suppressor Activity ◽  
Suppressor Factor ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Factor Production

Previous studies have shown that alloantigen-activated spleen T cells produce a soluble factor which suppresses mixed lymphocyte reaction proliferative responses, and that the interaction between suppressor and responder cells is controlled by genes of the H-2 complex. However a defect in the expression of suppressor activity was identified in the mouse strain C57BL/6J. Factor prepared from alloactivated B6 spleen cells failed to suppress MLR responses of syngeneic or H-2 compatible responder cells. Unimpaired suppressor factor production by other H-2 (b) strains and failure of suppressor factor production by a B6 congenic strain, B6.C-H-2(d) isolated the defective gene to the non-H-2 portion of the genome. In addition, the defect appeared to be related specifically to inability to produce an active factor, while the capacity to respond to suppressor molecules was unimpaired. The genetic character of the non-H-2 gene action was identified in F1 hybrid studies. Initially F(1) hybrids of the nondefective histoincompatible strains were studied. Suppressor factor from F1 cells suppressed the responses of both parental strains, and parental factors each suppressed the response of F(1) cells. Adsorption of F(1) factor with Con A-activated thymocytes of either parental strain removed suppressor activity specific for that strain, leaving activity against the other parental strain intact. The data support cedominant expression and production of distinct, parental H-2 haplotype-specific suppressor molecules by F(1) suppressor cells. An F(1) hybrid of the defective B6 strain with nondefective BALB/c produced suppressor factor which was also capable of suppressing both parental strains. Production of a suppressive B6-reactive factor by F(1) cells was verified by adsorption studies. Thus it appears that non-H-2 genes of the BALB/c parent acted in a genetically dominant fashion to provide the function required for expression of B6 suppressor molecules. We conclude that multiple genes control the expression of alloactivated suppressor cell activity, with at least one gene mapped to the I-C subregion of the murine major histocompatibility complex and one or more genes mapped to the non-H-2 gene complement.

scholarly journals Histocompatibility linked immune responsiveness and restrictions imposed on sensitized lymphocytes.

1977 ◽  
Vol 145 (6) ◽  
pp. 1623-1628 ◽  
Author(s):  
J F Miller ◽  
M A Vadas ◽  
A Whitelaw ◽  
J Gamble ◽  
C Bernard
Keyword(s):  
Major Histocompatibility Complex ◽  
Delayed Type Hypersensitivity ◽  
Immune Responsiveness ◽  
Gene Products ◽  
Region Gene ◽  
F1 Hybrid ◽  
Histocompatibility Complex ◽  
Hybrid Mice ◽  
Stable Structures ◽  
Ir Genes

Delayed-type hypersensitivity (DTH) transfer to GAT was restricted by the I-A region of the major histocompatibility complex (MHC). Sensitized cells from F1 hybrid mice between responder and nonresponder strains transferred DTH to syngeneic F1 mice and to naive parental strain recipients of the responder but not of the nonresponder haplotypes. These results are interpreted to favor the postulate that the MHC-linked Ir genes exert their effects by coding for components which allow interactions between particular I region gene products and the region to form stable structures immunogenic for DTH T cells.

Sign in / Sign up

Export Citation Format

Share Document