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J Klein

Publications and source records attributed to J Klein.

At least 757 records · Page 42Linked to original sources
PubMed1983

Cross-reactivity of suppressor T cells specific for lactate dehydrogenase B and IgG2a myeloma protein.

The major histocompatibility complex-controlled immune responsiveness of mice to two unrelated antigens, lactate dehydrogenase B (LDHB) and IgG2a myeloma protein is remarkably similar (1, 2). The similarity is explained by our recent work, demonstrating that both antigens, when presented in the context of cell surface Ek (Ek alpha Ek beta) molecules, generate strong suppression that causes nonresponsiveness to all mouse strains expressing this molecule. The suppression is mediated by antigen-specific, Ek-restricted Lyt-1+2+ suppressor T (Ts) cells, which act by inhibiting the proliferation of A(A alpha A beta)-restricted, Lyt-1+2- (possibly T helper [Th]) cells specific for the same antigen (3-5). However, the question of why the Ek molecule, in combination with two structurally unrelated proteins, preferentially induces Ts cells has remained unanswered. We demonstrate here that the anti-LDHB and anti-IgG2a Ts cells are fully cross-reactive, which indicates that the LDHB + Ek and IgG2a + Ek determinants recognized by these cells are very similar or identical.

Animals↗
PubMed1983

Complexity of the histocompatibility-3 region in the mouse.

Congenic lines C57BL/10Sn (H-3a), B10.LP-H-3b, B10.C-H-3c, and B10.KR-H-3d were arranged into the 12 possible recipient-donor combinations and immunized. The spleen cells of each recipient were then tested for the presence of cytolytic effector T lymphocytes (CTL) specific for antigenic determinants controlled by the H-3 locus and restricted by class I H-2 loci. The strain-distribution pattern of the determinants defined by the individual CTL was determined by direct testing and by cold-target inhibition analysis. The restriction elements of the individual determinants were identified by the testing of H-2 recombinant strains and by antibody blocking. Five determinants were identified: 1 and 2, restricted by the Db molecule; 3 and 4 restricted by the Kb molecule; and 5, for which the restriction molecule could not be determined. The distribution pattern of determinants 3 and 4 correlated with the distribution of alleles at the beta 2-microglobulin locus. The data could be interpreted as arguing for the existence of three loci in the H-3 complex, with one coding for mutually antithetical determinants 1 and 2, another coding for mutually antithetical determinants 3 and 4, and still another coding for determinant 5.

Animals↗
PubMed1983

The nature of the interaction between suppressor and helper T cells in the response to LDHB.

Purified Lyt-1+2+ T cells were depleted of alloreactive cells by BUdR and light treatment, and then were primed in vitro against LDHB presented on allogeneic APC. Such cells could be restimulated by LDHB on the same allogeneic APC, but not by LDHB on APC syngeneic with the T cells. The restimulated T cells suppressed the proliferative response of Lyt-1+2- T cells primed and restimulated by the same antigen. The suppression, which was antigen specific, occurred after a 6-hr co-culture of the suppressor (Tse) and proliferating helper (Th) cells. The successful interaction (as measured by suppression) between allogeneic Th and Tse cells was found to be determined by the restriction specificity but not the MHC haplotype of Th cells, and the MHC haplotype but not the restriction specificity of Tse cells. Thus, suppression occurred only when the Tse cells carried genes controlling the MHC molecules that served as restriction elements for antigen recognition by the Th cells. No evidence could be obtained for the participation of APC in the Tse-Th interaction. The data suggest the interaction is based on the recognition by the Th cell of the antigen presented in the context of MHC molecules controlled by the Tse cell.

Animals↗
PubMed1983

Induction of T cell responses in nonresponder mice by abolishing suppression with monoclonal antibodies recognizing A region-controlled, T cell-specific determinants.

Mouse strains carrying the kappa allele at loci A beta, A alpha, E beta, and E alpha are nonresponders to lactate dehydrogenase B (LDHB) and to allotypic determinants of IgG2a myeloma proteins (for example, UPC10 used in this study). The nonresponsiveness to these antigens is caused by T suppressor (Ts) cells that prevent antigen-primed T helper (Th) cells from proliferating. We demonstrate here that monoclonal antibodies specific for an A region-controlled molecule selectively expressed on T cells (A-T) are capable of inducing anti-LDHB and anti-UPC10 responses of primed T cells from nonresponder strains. A monoclonal anti-J antibody that cross-reacts with the A-T molecule also induces responsiveness, whereas another J-specific antibody that lacks this cross-reactivity fails to do so. The mechanism of response induction is blocking of the interaction between the Ts cell or its factor (TsF) and the target of suppression, the antigen-specific Lyt-1+2- (Th) cell. The blocking occurs at the level of the Ts cell and the TsF. The data indicate that Ts cells and TsF carry a unique, A region-controlled molecule that is not only functionally analogous but also serologically similar to the J molecule.

Animals↗
PubMed1983

Evidence for minor structural variations of class II genes in wild and inbred mice.

We organized 29 B10.W lines into eight antigenic groups on the basis of similarities in the antigenic phenotypes of their class II antigens. Tryptic peptide fingerprint comparisons of class II antigens in different antigenic groups detected structural variations in 30 to 60% of the tryptic peptides. In contrast, less than 10% of the tryptic peptides were distinguishable in comparisons of class II antigens within the same antigenic group. These results suggest structurally discrete allelic families of class II genes exist in wild mouse populations.

Animals↗
PubMed1983

The inactivation of hemostatic factors by hematin.

Prolonged clotting times and reduced levels of clotting factors have been reported in hematin-treated patients. This effect persists for up to 5 hr after hematin infusion, associated with plasma levels ranging from 0.01 to 0.04 mg/ml. Therefore we performed in vitro studies to investigate the effects of hematin on fibrinogen, thrombin, factor VIII:C, and plasmin. Hematin in a final concentration of 0.01 mg/ml inhibited the clotting of bovine fibrinogen (1.3 to 2.6 mg/ml) by bovine thrombin (0.12 U/ml) and inhibited the hydrolysis of a synthetic substrate by human thrombin. However, if the hematin was first mixed with albumin (25 mg/ml), fourfold higher concentrations were required to prolong the thrombin clotting time. Hematin, 0.035 mg/ml, reduced VIII:C activity from 0.88 to 0.40 U/ml as measured by two-stage assay. Hematin (0.05 mg/ml) also inhibited the activation of VIII:C by thrombin (0.04 U/ml): baseline activity, 0.84 U/ml; thrombin-activated, 2.94 U/ml; with hematin added, 1.33 U/ml. Hematin also inhibited clot lysis. The inclusion of hematin (0.03 mg/ml) in the diluting buffer reduced the lysis of whole blood clots from 86% +/- 5 to 23% +/- 5 (p less than 0.001, mean +/- S.D. of four determinations) and decreased the lysis of 125I-fibrin clots induced by plasmin (0.02 CTA U/ml) from 100% to 27%. In concentrations as low as 0.09 microgram/ml, hematin inhibited the hydrolysis of a synthetic substrate by plasmin. Hematin was mixed with fibrinogen, albumin, or thrombin, and the mixtures applied to Sephadex G-200 columns. Adherence of the hematin to Sephadex was prevented by either prerinsing the column with albumin or using borate buffer at pH 9.2. Hematin co-eluted with each protein applied to the column and, in the case of fibrinogen, altered its electrophoretic mobility and markedly prolonged the thrombin clotting time of the eluted fibrinogen. We conclude that hematin binds to a variety of hemostatic proteins, inhibiting their biologic activity.

Animals↗
PubMed1983

Frequency of responsiveness to the H-Y antigen among the B10.W lines.

B10.W females were immunized against syngeneic male cells (via the footpad and also i.p. in some strains) and their spleen cells were then restimulated in vitro and tested in the cell-mediated lympholysis assay for H-Y-specific killing of target cells. Only seven of the 33 tested lines were anti-H-Y responders. The effector cells obtained from each of the responder lines were then tested against male and female cells of other B10.W lines, as well as a number of classic B10 congenic lines, and the MHC molecules providing the context for H-Y recognition were identified. They were: Kk, Kw3, Kw7, Kw17, Kw27, Dk, and Dp. None of the strains generated effector cells capable of recognizing the H-Y antigen simultaneously in the context of the K and D molecules. The WOA1 females generated effector cells by using the Kw7 molecule for context of recognition, whereas the WR7 females produced cells recognizing the H-Y antigen exclusively in the context of the Dk molecule despite the fact that both lines share the Kw7 gene. Some of the effector cells cross-reacted with both male and female cells of other strains and this cross-reactivity could be attributed to the recognition of allogeneic MHC molecules controlled by K or D region genes. Interestingly, STA39 females generated Dp- but not Kw3-restricted anti-H-Y responses, whereas SAA48 females generated Kw3- but not Dw3-restricted responses; the Kw3-restricted cells cross-reacted with the Dp molecule. This cross-reaction might explain why the STA39 females do not mount a Kw3-restricted anti-H-Y response. Because the Kw3 + H-Y combination resembles Dp, the anti-Kw3 + H-Y T cells are functionally eliminated when tolerance of Dp molecules is attained in the STA39 mice.

Alleles↗
PubMed1982

H-2-controlled suppression of T cell response to lactate dehydrogenase B. Characterization of the lactate dehydrogenase B suppressor pathway.

We characterized the cell types involved in the H-2-controlled suppression of T cell response to lactate dehydrogenase B (LDHB). The suppressor effector (Tse) was found to be an Lyt-1+2+, J+ cell that recognizes antigen together with Ek molecules of antigen-presenting cells (APC). To become functional, the Tse cell requires a second signal from a nonspecific, Lyt-1+2-, J+ suppressor-inducer (Tsi) cell. The Tsi-Tse interaction is not subject to any genetic restriction. The target cell of suppression is an Lyt-1+2-, J- (most likely T helper [Th]) cell that recognizes LDHB in the context of A molecules on APC. The suppression is manifested in inhibition of the antigen-specific, A-restricted proliferation of Th cells. The interaction between Tse and Th is restricted by the A region of the H-2 complex. Because this restriction is determined by the receptor of Th cells, the mechanism of Th-Tse interaction most likely involves a concomitant recognition of LDHB and A region-controlled molecules by Th cells on the surface of Tse cells.

Animals↗
PubMed1982

Restriction molecules involved in the interaction of T cells with allogeneic antigen-presenting cells.

The proliferative responses of T cells, depleted of alloreactive cells, were tested upon stimulation by antigens presented on allogeneic antigen-presenting cells (APC). Restriction molecules involved in these responses were identified by inhibition of T cell proliferation with monoclonal antibodies against A(A alpha A beta) and E(E alpha E beta) molecules of the APC. The responses to all three antigens tested [Poly(Glu40Ala60) (GA), lactate dehydrogenase B (LDHB), and poly(Glu51, Lys34, Tyr15) (GLT)] were A plus E restricted when the allogeneic APC expressed both molecules, and only A restricted when the APC did not express cell surface E molecules. In contrast, when T cells and APC are syngeneic, the same antigens are recognized only in the context of either A molecules (GA and LDHB) or E molecules (GLT). The data indicate that the immune response gene control of these responses is not associated with either a failure of antigen presentation, or the lack of certain T cell specificities from the germ line repertoire, but probably with selective somatic elimination (tolerance) of certain clones from the T cell repertoire.

Animals↗
PubMed1982

Suppression of cell-mediated lymphocytotoxicity against minor histocompatibility antigens mediated by Lyt-1+Lyt-2+ T cells of stimulator-strain origin.

Cultured, unprimed spleen cells suppress the generation of cytolytic T lymphocytes when added to mixed lymphocyte culture of cells disparate at minor histocompatibility (H) loci. Cells cultured for 2 to 3 days inhibit cell-mediated lympholysis specifically in that they suppress only when they carry the same H antigen by which the stimulators activate the responding cells. However, culturing of cells for more than 3 days results also in the generation of nonspecific suppressor cells which inhibit the cell-mediated lympholysis regardless whether they carry the stimulating antigens. The specific suppressor cells are T lymphocytes of the Lyt-1+Lyt-2+ type. Fresh, uncultured spleen cells, although ineffective in vitro, can prevent the in vivo priming of minor H-specific cytotoxic T lymphocyte precursors when injected i.v. into mice incompatible at minor H loci. This suppressive effect of the immunizing inoculum is abolished by irradiation (3300 rds) or by treatment with a monoclonal Thy-1-specific antibody and complement. Thus the suppressor T cell demonstrated here is of the "veto" cell type; that is, it probably suppresses minor H-specific cells when the latter recognize the stimulating antigen on the surface of the suppressor cell itself.

Animals↗
PubMed1982

Cytolytic T cells activated by H-2-controlled E molecules cross-react with A molecules.

Cell-mediated lymphocytotoxicity was generated in four strain combinations differing only by the cell-surface expression of the class II E molecule controlled by the H-2 complex. The four combinations were: B10.D2(R107) anti-B10.A(3R), B10.A(4R) anti-B10.A(2R), B10.GD anti-B10.D2(R101), and B10.S(7R) anti-B10.S(9R). In all four of these combinations, the stimulator expresses E molecules on the cell surface, while the responder does not. The cytolytic T lymphocytes generated in the B10.D2(R107) anti-B10.A(3R) and B10.A(4R) anti-B10.A(2R) combinations reacted not only with the stimulator but also with strains that do not express cell-surface E molecules, in particular, strains carrying the H-2f and H-2q haplotypes. The cross-reactivity with E-negative strains could be blocked by monoclonal antibodies specific for the Af or Aq molecules but not by antibodies recognizing determinants on E or class I (K) molecules. The anti-H-2f cross-reactivity could be inhibited by H-2q cold targets and, reciprocally, the anti-H-2q reactivity could be blocked by H-2f cold targets. These findings are interpreted as indicating that the cytolytic T lymphocytes stimulated by E molecules can recognize and lyse cells lacking E molecules but expressing A molecules. The observed E-A cross-reactivity supports the notion of structural and functional relatedness between the A and E molecules and suggests a common evolutionary origin of the A- and E-encoding loci.

Animals↗