Genetic analysis of immune suppression

We have analyzed the genetic control of susceptibility to suppression by 1-J⁺, suppressor-T-cell derived factors (TsF) specific for the synthetic polymer L-glutamic acid⁵⁰-L-tyrosine⁵⁰ (GT). GT-TsF activity was measured as specific inhibition of proliferative responses to GT developed in cultures of lymph-node T cells from mice primed with GT complexed to methylated bovine serum albumin (GT-MBSA). These experiments demonstrated that there is no MHC-encoded genetic restriction between donors and recipients of GT-TsF in suppression of proliferative responses. We have also confirmed the observations that mice of the H-2 ^b, H-2 ^d, and H-2 ^khaplotypes can produce GT-TsF, whereas H-2 ^amice do not, and that H-2 ^b, H-2 ^d, and H-2 ^kmice are sensitive to GT-TsF from all producer strains, whereas H-2 ^bmice are not sensitive to GT-TsF from any strain. Analysis of the effect of GT-TsF on responses by mice bearing recombinant haplotypes suggests that at least two genes are required for susceptibility to GT-TsF and that these genes show coupled complementation.Abbreviations used in this paper GAT random linear terpolymer of L-glutamic acid⁶⁰-L-alanine³⁰-L-tyrosine¹⁰ - GAT-MBSA GAT complexed to methylated bovine serum albumin - GATTsF GAT-specific-T-cell derived suppressor factor - GT random linear copolymer of L-glutamic acid⁵⁰-L-tyrosine⁵⁰ - GT-MBSA GT complexed methylated bovine serum albumin - GT-TsF GT, specific, T-cell derived suppressor factor - ³H-TdR tritiated thymidine - Ir gene immune response gene - MBSA methylated bovine serum albumin - MEM minimal essential media - MHC major histocompatibility complex - PFC plaque-forming cell(s) - PPD purified protein derivative of M. tuberculosis H37Ra     

Recombination between genes coding for immune response and the serologically determined antigens in the chickenB system

Evidence is presented for a crossover between the genes coding for the serologically determined (SD) antigens on erythrocytes and an immune response gene (Ir-GAT) controlling immune response to the synthetic polypeptide GAT within theB complex, the MHC of chickens. TheIr-GAT ¹ andIr-GAT ¹⁹ alleles control low and high immune response to GAT, respectively. Both low and high responders were recovered as recombinants fromB ¹ B ¹ andB ¹⁹ B ¹⁹ birds. The low-responder haplotypes are homozygous for theIr-GAT ¹ allele and the high-responder haplotypes carry theIr-GAT ¹⁹ allele. Mortality forB ¹ B ¹ nonresponder birds was 39%, compared with 19% for theB ¹ B ¹ high responders; this suggests the possibility that genes located within the immune response region of theB complex exert some genetic control over viability and survival.The following abbreviations are used in this paper MHC major histocompatibility complex - Ir immune response - SD serologically determined - GA (L-glutamic acid⁶⁰, L-alanine⁴⁰) n - DNP-GL dinitrophenyl-(L-glutamic acid⁶⁰, L-lysine⁴⁰) - PLL poly-L-lysine - (T,G)-A--L poly-(L-tyrosine-L-glutamic acid)-poly-D, L-alanine-poly-L-lysine - GAT, GAT¹⁰ (L-glutamic acid⁶⁰ L-alanine³⁰ L-tyrosine¹⁰) n - CFA complete Freund's adjuvant - PBS phosphate-buffered saline     

Immune response genes in chickens

The immunogenecity in chickens of the synthetic polypeptide TGAL is shown to be highly batch-dependent. Antibodies of at least two quite different specificities were formed: an MHC-linked anti-TG response, and a non-TG response (probably to poly-alanine) which is not linked to the MHC. Immunization with the random copolymer GT also gave rise to an anti-TG antibody response which showed a firm linkage to theB complex. It is concluded that GT may serve as a useful marker for an MHC-linked gene in chickens. Surprisingly, conjugation of GT to the immunogenic carrier MBSA did not convert low GT responder chickens to high responders. This finding raises the possibility that the low responder status may be the result of specific suppressor cells.     

Genetic control of T-cell proliferative responses to poly(glu40ala60) and poly(glu51lys34tyr15): Subregion-specific inhibition of the responses with monoclonal Ia antibodies

The relationship betweenIr genes and Ia antigens was studied in the T-cell proliferative responses to two synthetic polypeptides poly(glu⁴⁰ala⁶⁰) (GA) and poly(glu⁵¹lys³⁴tyr¹⁵) (GLT¹⁵). The response to GA was found to be controlled by anIr gene in theI-A subregion, whereas the anti-GLT¹⁵ response was shown to be under dual control, oneIr gene mapping probably in theI-A subregion, and the other in theI-E subregion. We obtained two different lines of evidence suggesting identity ofIr and Ia genes. First, the presence of certain serologically identified allelic forms of the I-A-encoded A molecule correlated with the responder status to GA both in inbred strains and in B10.W lines, the latter carrying wild-derivedH-2 haplotypes. Thus the Ir and Ia phenotypes were not separable in strains of independent origin. Second, the anti-GA response was completely inhibited by monoclonal antibodies against determinants on the A molecule (Ia.8, 15, and 19), but not by a monoclonal antibody against a determinant on the E molecule (Ia.7). In contrast, the anti-GLT¹⁵ response was only inhibited by a monoclonal antibody against the E molecule, but not by antibodies against the A molecule. Our data support the hypothesis that Ia antigens, as restriction elements for T-cell recognition, may in fact be the phenotypic manifestation ofIr genes.     

Mechanisms of genetic control of immune responses

The mechanisms underlying Ir gene control of CMI were addressed by examining the DTH and Tprlf responses specific for the synthetic polymers GT, GAT, and GA. We show that BALB/c mice (GAT/GA responders, GT nonresponders) primed with GT fail to develop DTH and Tprlf responses specific for GT, GAT, or GA. GAT immunization resulted in DTH responses that could be elicited not only with GAT and GA but also with GT, demonstrating that GT-specific T_DH are present in nonresponder mice. GT-specific DTH was transferred with Thy-1⁺ Lyt-1⁺2^–, H-2 Irestricted, nylon wool nonadherent cells. GA-primed BALB/c mice developed GAT- and GA-, but not GT-apecific DTH responses, indicating that GA and GT do not cross-react at the T-cell level. The ability of GAT [but not a mixture of GA plus GT, or GT electrostatically complexed to the immunogenic carrier MBSA (GT-MBSA)] to induce GT-specific DTH suggested a requirement for covalent linkage of stimulatory GA and nonstimulatory GT determinants present on the GAT molecule. Similarly, GT-specific in vitro Tprlf responses could be demonstrated in GAT-primed mice exhibiting significant levels of GT-specific DTH but not in GT- or GT-MBSA-primed mice. Tolerization experiments also suggested that GT-specific Th were involved in the development of GT-specific DTH in GAT-primed mice. The GT nonresponsiveness of BALB/c mice for DTH and Tprlf responses could not be reversed by treatments designed to abrogate Ts activity (priming with GT-MBSA and CY injection), nor could GT-primed cells be shown to inhibit the development or elicitation of GT-specific CMI in GAT-primed mice during the afferent and/or efferent stages of DTH. Our results suggest that GT nonresponsiveness does not result from the absence of GT-specific T cells or preferential induction of Ts. The results are discussed in the context of hole-in-the-repertoire and antigen presentation (determinant selection) models of Ir gene control.Abbreviations used in this paper APC antigen-presenting cells - BSA bovine serum albumin - BSS Mishell-Dutton balanced salt solution - CFA complete Freund's adjuvant - CMI cell-mediated immunity - CY cyclophosphamide - DTH delayed-type hypersensitivity - GA poly(Glu⁶⁰Ala⁴⁰) - GAT poly (Glu⁶⁰Ala³⁰Tyr¹⁰) - GT poly(Glu⁵⁰Tyr⁵⁰) - GT-MBSA GT complexed to methylated bovine serum albumin - It immune response - LN lymph node - PPD purified protein derivative of tuberculin - TDH DTH T cells - Th helper T cells - Tprlf T-cell proliferation - Ts suppressor T cells - TsF T-cell suppressor factor(s)     

Idiotypic analysis of anti-GAT antibodies. III. Determinant specificity and immunoglobulin class distribution of CGAT idiotype.

The humoral response to poly-(L-glutamic acid60, L-alanine 30, L-tyrosine10), GAT, in mice is further characterized by both idiotype and fine specificity analyses. The common idiotype on murine anti-GAT antibodies (CGAT) was identified in anti-GAT antisera from seven additional strains of mice. These data confirm that the CGAT idiotype can be induced in all inbred strains of mice. Using a partially inbred strain of mice selected for their ability to respond to poly-(L-glutamic acid50, L-tyrosine50), GT, we demonstrated that the GT copolymer is capable of inducing antibodies that express the CGAT idiotype. In contrast, antisera directed against poly-(L-glutamic acid60, L-alanine40), GA, bind GAT but lack CGAT idiotype. These results indicate that GAT molecules contain determinants either similar or identical to those on GT molecules, which are responsible for the induction of CGAT idiotypic antibodies. We also demonstrated that both GAT responder and nonresponder strains of mice can produce anti-GAT antibodies with similar fine specificity patterns and CGAT idiotype. In addition, we demonstrate that antibodies of the IgM, IgG1, and IgG2 immunoglobulin classes express the CGAT idiotype.     

Immune response genes in inbred rats. I. Analysis of responder status to synthetic polypeptides and low doses of bovine serum albumin

The immune responses of nine inbred rat strains to a high dose of the synthetic copolymers GT, GA or GAT and of eight strains to low doses of BSA were compared. The strains tested represent six known haplotypes of the major histocompatibility locus in rats. The studies allowed a clear differentiation of the rat strains into high and low or nonresponders for GT and GA according to the levels of specific antibodies produced after primary and secondary immunization with these antigens and specific delayed type hypersensitivity reactions. A considerably less clear responder — non (or low) responder distribution pattern among the rat strains was found for GAT and low doses of BSA. The genetic background for the observed phenotypes and a possible relationship between responder status and the major histocompatibility locus are discussed.     

RT1-Linked Ir and Is genes control the immune response to bovine insulin in the rat

The immune response to bovine or pork insulin (BI or PI, respectively) was studied in the rat using the in vitro insulin-induced lymphocyte-proliferation assay. Results indicated that 11 inbred rat strains were divided into categories of high and low responders. Two high responders, SDJ (RT1 ^u) and BN(RT1 ⁿ) inbred rat strains, appeared to recognize different antigenic determinant(s) on the insulin molecule. The results of linkage and segregation analyses in F₁, F₂, backcross, and partially congenic rats showed that the Ir gene (Ir-BI), which encodes the high responsiveness in the SDJ rats, is inherited associated with RT1 ^u, whereas the immune suppression gene (Is-BI), which encodes the low responsiveness in the WKA(_RT1 ^k) rats, is inherited together with RT1 ^k. The Is-BI is the first major histocompatibility complex (MHC)-linked Is gene reported in the rat. The LEJ(RTI-A ^u B ^b) inbred rat strain showed a low response to BI, indicating that Ir-BI is closer to RTI-B/RTI-D region than to RTI-A.Abbreviations used in this paper BI bovine insulin - HEPES N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid - It immune response - Is immune suppression - MHC major histocompatibility complex - mol. wt. molecular weight - PI pork insulin - sc subcutaneously - SD standard deviation - SI stimulation index     

Genetic control of the primary humoral response to Glu56Lys35Phe9

The primary humoral responses of mice to the linear random terpolymerl-Glu⁵⁶-l-Lys³⁵-l-Phe⁹ (GLø) were studied, utilizing the Farr antigen-binding technique and a new hemagglutination assay. This new hemagglutinin assay was easier and more convenient than the conventional Farr method, and was more sensitive in detecting early IgM responses. Following primary immunization, the majority of antibodies produced by responder strains were 2-ME-sensitive. These 2-ME-sensitive antibodies chromatographed at the same relative position as IgM on a Sepharose 6B column. On the other hand, no antibodies of either the IgM or IgG class could be detected in nonresponder strains. These data are consistent with the hypothesis that two complementingIr genes are required for the primary IgM response to GLø, in contrast to findings previously reported for (T,G)-A — L, anotherH-2-linked, complementing,Ir gene system. The implications of these differences are discussed.     

Genetic analysis of the non-H-2-linked Ir genes controlling the cytotoxic T-cell response to H-Y in H-2 d mice

The T-cell mediated immune responses to the male specific minor histocompatibility antigen H-Y in mice have been studied extensively as a model for immune responses to other weak antigens like tumor antigens or autoantigens. In a recent analysis of the strain distribution of the cytotoxic T-cell (Tc-cell) responsiveness to H-Y, it has been found that genes both within and outside the H-2 complex exert an interactive control. Whereas the H-2 ^b strains all are high responders, independent of their non-H-2 background, other H-2 haplotypes (d, k, and s) only allow for a response if they are combined with certain non-H-2 genes. The H-2-linked immune response genes (Ir-genes) have been previously mapped to the I and K or D region of the H-2 complex, but the mapping of the non-H-2 genes has not yet been established. In this study evidence is presented, using recombinant inbred strains and immunoglobulin heavy chain (Igh) congenic strains of mice, to show that there is more than one non-H-2 Ir-gene involved, that the main controlling genes are not linked to the Igh complex, and that at least one non-H-2 Ir-gene is linked to the H-3 region on chromosome 2. This region includes genes for beta-2-microglobulin (2m), the Ly-mllalloantigen a polymorphic cell surface glycoprotein (Pgp-1), a B-cell specific antigen Ly-4, a transplantation antigen H-3, and genes (Ir-2) controlling the immune response to Ea-1 and H-13.     

Immunosuppressive factor(s) specific for L-glutamic acid50-L-tyrosine50 (GT). I. Production, characterization, and lack of H-2 restriction for activity in recipient strain.

The random synthetic copolymer of L-glutamic acid50-L-tyrosine50 (GT) fails to elicit a GT-specific antibody response in all inbred strains of mice tested. Preimmunization with GT specifically inhibits a GT-MBSA response in certain H2d,k,s, but not other, H-2a,b,q, nonresponder mice. This unresponsiveness is mediated by GT-specific suppressor T cells. Extracts prepared from lymphoid cells of GT-primed suppressor haplotype mice inhibit the development of primary GT-specific antibody responses to GT-MBSA in normal syngeneic mice. Nonsuppressor haplotype mice do not produce GT-specific suppressor factor. The GT-suppressive extract has affinity for antigen and a m.w. of less than 50,000 daltons, thus, resembling antigen-specific immunosuppressive factors already described. However, the GT-suppressive extract does not appear to have H-2 restrictions since it works across allogeneic barriers. Evidence is presented that two genes are required for factor-mediated suppression.     

Two distinct high immune response phenotypes are both controlled byH-2 genes mapping inK orI-A

Murine responses to immunization with 2, 4, 6-trinitrophenyl (TNP) conjugated to autogenous mouse serum albumin (MSA) in complete Freund's adjuvant (CFA) are controlled by a gene(s) in theK orI-A region of theH-2 complex. High immune responses of bothH-2 ^d andH-2 ^b mice have been mapped to this region of the major histocompatibility complex. No modifying effects were observed from genes to the right ofI-A in either responder haplotype. High responsiveness controlled byK ^b orI-A ^b is inherited with complete or partial recessivity, depending on the route of immunization and the sex of the responder. However, high responsiveness controlled byK ^d orI-A ^d is inherited dominantly. This unusual pattern of inheritance of immune responsiveness to TNP-MSA is consistent with the genetic mapping toK orI-A. TNP-MSA-specific T-cell reactivity following immunization with TNP-MSA in vivo was examined utilizing a T-cell-dependent proliferation assay in vitro with cells obtained from high or low responder mice. Genetic mapping and mode of inheritance in this assay for antigen-specific T-cell reactivity corresponded with results obtained from a plaque-forming cell (PFC) assay measuring antibody production by B cells. Both the proliferative and PFC responses are probably under the sameIr gene control. Both gene dosage effects and Ir-gene-product interaction could influence the generation of specific immune responsiveness in F₁ hybrids between high and low responders to TNP-MSA.     

The structural genes of internal invertases in Saccharomyces cerevisiae.

Summary Polyacrylamide gel electrophoresis (without SDS) of invertases from strains each carrying only one of the five known SUC-genes revealed differences in mobility of the internal enzymes. SUC1 invertase moved distinctly slower than the invertases formed in the presence of genes SUC2 to SUC5. Three bands of internal invertase activity were found in diploids carrying both SUC1 (slow invertase) and one of the other SUC-genes (fast invertases). Tetrad analysis of such diploids yielded haploids which showed the same three bands if they carried SUC1 in combination with another SUC gene. A gene dosage effect was observed in relation to invertase activity in haploid strains with only gene SUC1 or only SUC4 on one hand, and both genes on the other hand. A sucrose non-fermenting and invertase negative strain with mutant allele suc3-3 of gene SUC3 (fast invertase) was crossed with SUC1. The heterozygous diploid and the recombinant haploids (SUC1 suc3-3) showed two bands in the region of the internal invertase: a slow SUC1 band and a second band corresponding to the intermediate band of SUC1-SUC3 strains. The intermediate band in SUC1 suc3-3 strains is considered as a hybrid consisting of an active SUC1-monomer and an inactive suc3-mutant monomer. Formation of such hybrid bands was taken as evidence for the structural nature of SUC-genes.     

Genetic chasing of T helper cell idiotype and allotype genes

The present experiments were performed to study whether the genes responsible for the expression of T-cell idiotypes and allotypes could be mapped in relation to immunoglobulin (Ig) heavy chain V- and C-genes. Use was made of our antiserum 5936, which detects idiotypes in B6 anti-B10.BR sera and on Lyt-1⁺, 2.3^–B6 anti-B10.BR T-cell populations, and antiserum 6036, which detects allotypes on Lyt-1⁺, 2.3^–B6 T cells, but which does not react against Ig. The reactivity of these antisera with T cells from (B6 x C3H.OH) x C3H.OH backcross mice and CBA-allotype congenic B6 mice was investigated because 5936 idiotypes and 6036 allotypes appeared to be associated with Igh-1 ^b genes (B6) and not with Igh-1 ^b genes (C3H.OH, CBA). Our results will show, first, that 5936 idiotypes on Lyt-1⁺, 2.3^–B6 anti-B10.BR T cells are synthesized by genes linked to Igh-1 ^b allotype genes and they are situated either within Ig heavy chain V-genes or centromeric to them. Second, our results will show that 6036 allotypes on Lyt-1⁺, 2.3^–B6 T cells are produced by genes also linked to Igh-1 ^b -allotype genes, and the 6036 allotype genes are situated between Ig-VH and prealbumin genes.Abbreviations used in this paper BCGF B cell growth factor - B6 C57B1/6 - C_H constant region of immunoglobulin heavy chain - Con A concanavalin A - FCS fetal calf serum - Id idiotype - Ig immunoglobulin - LPS lipopolysaccharide - M mouse - MHC major histocompatibility complex - MLC mixed lymphocyte culture - MRBC mouse red blood cells - NMS normal mouse serum - NP nitrophenacetyl - NRS normal rabbit serum - PFC plaque forming cell - R rabbit - Tcf T cell factor - Tcr T cell receptor - TNP Trinitrophenol - V_H variable region of Ig heavy chain Definitions of terms used in this paper: T-cell idiotypes, structures on T-cell membranes or released T-cell molecules detected by an anti-idiotypic antiserum (5936) produced against specific immunoglobulin idiotypes. The 5936 T-cell idiotypes are related to the specific binding of IA^k gene products by certain Igh-1^b T cells. T cell allotypes, structures on T-cell membranes or released T-cell molecules detected by an antiserum (6036) produced against 5936 idiotype-bearing T-cell molecules. The 6036 T-cell allotypes are related to the binding by Igh-1^b T cells of all Ia gene products tested, and they are non-cross-reactive with immunoglobulin allotypes.     

Cross-stimulation of antigens under separate histocompatibility-linkedIr gene control

The antibody response of rats to the related polypeptide antigens (T,G)-A —L, (H,G)-A -L, and (Phe,G)-A -L is controlled byIr gene(s) linked to the major histocompatibility genes. When lymph node cells of rats primed with one of these polypeptides were cultured with the homologous antigen, a proliferative secondary response was induced with cells from high, but not from low responder strains. Thus, responsiveness as defined by antibody production is clearly reflected in this cellular in vitro assay.In contrast to the antipolypeptide antibodies which crossreact extensively, no crossreaction could be detected on the cellular level among the three polypeptides except for one combination: (T,G)-A -L-primed cells were strongly cross-stimulated by (Phe,G)-A -L, but the opposite was not true. The two antigens, however, show a distinct response pattern in various rat strains. The unilateral cross-stimulation may be explained by the special chemical relationship of determinants containing tyrosine and phenylalanine residues. It could occur on the level of the T cell receptor or, if distinct from it, on that of theIr gene product.Abbreviations used in this paper are as follows GT linear copolypeptide, poly (L-Glu, L-Tyr) - (T,G)-A-L the branched synthetic polypeptides poly(L-Tyr, L-Glu)-poly-DL-Ala-polyL-Lys - (H,G)-A -L the branched synthetic polypeptides poly(L-His, L-Glu)-poly-DL-Ala-poly-L-Lys - (Phe,G)-A-L poly(L-Phe, L-Glu)-poly-DL-Ala — poly-L-Lys - i.m. intramuscularly - LDH_A lactate dehydrogenase, isozyme A - MBSA methyl ester of bovine serum albumin - PHA phytohemagglutinin ofPhaseolus vulgaris     

Molecular events in the processing of avidin by antigen-presenting cells (APC)

The immune response of T lymphocytes to avidin was measured by proliferative assays, antibody production and delayed-type hypersensitivity. Mice ofH-2 ^k haplotypes were found to be low responders, whereas mice of other haplotypes, and particularly ofH-2 ^s , were high responders.Ir genes controlling this response were mapped to theI subregion ofH-2. Helper T cells were found to be responsible for the Ir phenotype of antibody production. These results indicate the feasibility of using the avidin-biotin complex as a tool for studying molecular mechanisms by which antigens underIr gene control are processed and presented to T lymphocytes.Abbreviations used in this paper Ir genes, immune-response genes - H-2 murine major histocompatibility complex - APC antigen-presenting cell - OA ovalbumin - BSA bovine serum albumin - DNP dinitrophenyl - DNP-OA DNP-ovalbumin - DNP-Av DNP-avidin - DNP-BSA DNP-bovine serum albumin - CFA complete Freund's adjuvant - PPD purified protein derivative - PBS phosphatebuffered saline - IP intraperitoneal - LNC lymph-node cells - DTH delayed-type hypersensitivity     

The genetic control of the immune response to murine histocompatibility antigens

The genetic control of the immune response to H-4 histocompatibility alloantigens is described. The rejection of H-4.2-incompatible skin grafts is regulated by anH-2-linkedIr gene. Fast responsiveness is determined by a dominant allele at theIrH-4.2 locus. TheH-2 ^b ,H-2 ^d , andH-2 ^s haplotypes share the fast response allele;H-2 ^a has the slow response allele. Through the use of intra-H-2 recombinants, we have mapped theIrH-4.2 locus to theI-B subregion of theH-2 complex; theH-2 ^h4 ,H-2 ¹⁵, andH-2 ^t4 haplotypes are fast responder haplotypes. These observations suggest that the strength of non-H-2 histocompatibility antigens is ultimately determined by the antigen-specific recipient responsiveness.     

The influence of mutated genes on sporogenesis

Summary The course of meiosis in higher plants is controlled by a large number of genes, the function of which can be discerned by means of mutants showing any kind of meiotic anomaly. In general, there are three main groups of genes belonging to this system. The as-genes control the pairing behaviour of the homologous chromosomes, causing asynapsis in the mutated condition. The ds-genes are responsible for chiasma formation and chiasma frequency, causing desynapsis in the mutated condition. As- and ds-genes influence micro- and macrosporogenesis in a similar way but the ms-genes become effective only in microsporogenesis, resulting in a complete breakdown of meiosis at a stage specific for each gene of the group.In Pisum sativum, 58 mutants showing genetically conditioned meiotic anomalies have been cytogenetically analysed: 34 of them belong to the ds- and 7 to the as-group; one gene causes asynaptic as well as desynaptic effects; 13 genotypes are male sterile due to degeneration of the chromosomes; the remaining 3 genes cause less specific meiotic disturbances. The lethality of a mutant can be overcome by distinct environmental conditions but the mutant is sterile because of manifold meiotic anomalies.One gene in the Pisum genome controls the transition from the vegetative to the reproductive stage of the plants. Other genes influence the differentiation of the growing points in such a way that the sporogenic tissues are not formed. In these mutants, no sporocytes are present which can undergo meiosis.From the findings available for many species of the plant kingdom, it can be assumed that hundreds of genes controlling meiosis are present in the genome of each higher plant.The investigations were supported by the Ministry of Research and Technology of the Federal Republic of Germany and by the European Atomic Community.     

In vitro anti‐enterovirus 71 activity of gallic acid from Woodfordia fruticosa flowers

Aims: The anti‐enterovirus 71 (EV71) activity of six Nepalese plants’ extracts and gallic acid (GA) isolated from Woodfordia fruticosa Kurz (family; Lythaceae) flowers were evaluated in Vero cells. Methods and Results: The anti‐EV71 activity of tested compounds was evaluated by a cytopathic effect reduction method. Our results demonstrated that flowers’ extracts of W. fruticosa exerted strong anti‐EV71 activity, with a 50% inhibitory concentration (IC₅₀) of 1·2 μg ml^?1 and no cytotoxicity at a concentration of 100 μg ml^?1, and the derived therapeutic index (TI) was more than 83·33. Rivabirin showed no antiviral activity against EV71. Furthermore, GA isolated from W. fruticosa flowers exhibited a higher anti‐EV71 activity than the extract of W. fruticosa flowers, with an IC₅₀ of 0·76 μg ml^?1 and no cytotoxicity at a concentration of 100 μg ml^?1, and the derived TI was 99·57. Conclusions: This study demonstrated that flower extracts of W. fruticosa possessed anti‐EV71 activity and GA isolated from these flowers showed stronger anti‐EV71 activity than that the extracts. Significance and Impact of the Study: Our results suggest that the GA from W. fruticosa flowers may be used as a potential antiviral agent.     

Elimination of self-tolerogen turns nonresponder mice into responders

Two sets of genes control the immune response ofH-2 ^d mice to the synthetic antigen poly(Glu⁵⁰Tyr⁵⁰) (GT). One set involves class II major histocompatibility complex (Mhc) loci encoding an A^d product that serves as a recognition context to GT-reactive helper T cells (T_h). The other one is a background gene, the product of which, in association with the same Mhc-restricting element, mimics the GT/A^d complex. Mice expressing the GT-mimicking background-encoded structure (Im^gt), which is preferentially displayed on B lymphoblasts, do not respond to GT as a consequence of self-tolerance. On the other hand, elimination of cells bearing Im^gt renders these mice responsive to GT, demonstrating that tolerance to self can impoverish the immune system. Im^gt is probably not identical to GT, but resembles it in the way it forms complexes with A^d molecules ofMhc.