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R Hamers

Publications and source records attributed to R Hamers.

At least 73 records · Page 4Linked to original sources
PubMed1987

Nonrandom allele associations between unlinked protein loci: are the polymorphisms of the immunoglobulin constant regions adaptive?

Consistent linkage disequilibrium was observed between independently segregating protein loci. In natural populations of the European rabbit Oryctolagus cuniculus, highly significant, nonrandom associations between alleles of the constant regions of the immunoglobulin light and heavy chains were found, both within localities and between localities. We suggest that the population genetic data presented here are relevant to the adaptive significance of the genetic polymorphisms of the antibody constant regions.

Alleles↗
PubMed1986

Minichromosomal variable surface glycoprotein genes and molecular karyotypes of Trypanosoma (Nannomonas) congolense.

Employing orthogonal-field-alternation gel electrophoresis (OFAGE), we have separated chromosome-sized DNA molecules from Trypanosoma (Nannomonas) congolense clones, the clones being derived from several distinct antigenic repertoires. Trypanosome clones that belong to a specific antigenic repertoire appear to have a chromosome pattern characteristic of that particular repertoire. Hybridization of the separated chromosomes with cloned DNA fragments encoding variable surface glycoproteins revealed the presence of two different T.(N.) congolense variable surface glycoprotein genes on mini-chromosomes (mc) and the modes by which these genes may be activated: one by duplicative and the other by non-duplicative activation.

Animals↗
PubMed1986

Evidence for genetic diversity in Trypanosoma (Nannomonas) congolense.

Genetic proximity between two karyotypic groups of Trypanosoma congolense was investigated using as hybridization probes: total genomic DNA, a 35 nucleotide long synthetic oligonucleotide, and non-variant antigen type (non-VAT) specific complementary DNAs. The phylogenetic relationship between Trypanosoma brucei and T. evansi, both of which are accepted species in the subgenus Trypanozoon, was used as a reference to assess the phylogenetic proximity of the two groups of T. congolense. Results indicate that some morphologically indistinguishable T. congolense populations differ in a variety of molecular and genetic properties: molecular karyotypes, majority of the DNA sequences, and the restriction enzyme sites in the genomic environments of various conserved genes. The implications of these findings for trypanosome evolution and T. congolense epidemiology are discussed.

Animals↗
PubMed1986

Active suppression of interleukin 2 secretion in mice infected with Trypanosoma brucei AnTat 1.1.E.

Impairment of T cell proliferation in mice infected with the pleomorphic Trypanosoma brucei AnTat 1.1 E clone was found not to be related to a depletion of T cells or to an absence of functional accessory cells, but rather to an active suppression of interleukin 2 (IL-2) production. Lymph node cells derived from infected mice failed to produce IL-2 following Con A stimulation, whereas an exogenous supply of recombinant IL-2 could restore the impairment of the mitogen (Con A)-induced proliferative responses. Furthermore, lymph node cells derived from infected mice suppressed both secondary T-cell proliferative responses and IL-2 secretion, indicating that the trypanosome-induced suppression is mediated by a suppressive cell which interferes at the level of IL-2 secretion.

Animals↗
PubMed1985

Trypanosoma (Nannomonas) congolense: identification of two karyotypic groups.

Orthogonal-field-alternation gel electrophoresis and DNA blot hybridizations have been used to investigate the genomic relationships among trypanosome clones of subgenus Nannomonas. The results indicate that Trypanosoma (Nannomonas) congolense comprises at least two distinct groups of parasites that differ in both molecular karyotype and repetitive DNA sequences. A description of these two groups and their distinction from Trypanosoma (Nannomonas) simiae is presented.

Animals↗
PubMed1985

Assembly of oligonucleosomes into a limit series of multimeric higher-order chromatin structures.

Chicken erythrocyte chromatin, obtained after fragmentation with micrococcal nuclease, appears to remain folded in a stable distribution of supranucleosomal structures in buffers containing 80 mM NaCl. These supranucleosomal particles are composed of on average 25 nucleosomes. However, the integrity of the linker DNA within these particles is not required. The supranucleosomal particles have been interpreted by others as superbeads cut out of a preexisting granular nominal 30-nm chromatin fibre. We show that the same distribution of supranucleosomal structures (even those containing internal DNA scissions) can be reconstituted from unfolded nuclear chromatin extracts as present in 10 mM or 600 mM NaCl. Moreover, fractions of oligonucleosomes with mean lengths between 6 and 15 nucleosomes reassemble or aggregate into a limit series of multimeric species. The existence of an assembly barrier could be inferred as we were unable to observe a stable and soluble assembly product containing more than about 25 nucleosomes. We propose an alternative explanation for the generation and observation of a constant distribution of supranucleosomal structures in nuclear extracts, based on the assembly or aggregation property of oligonucleosomes and on the existence of an assembly barrier.

Animals↗
PubMed1985

Cloning and analysis of Trypanosoma (Nannomonas) congolense ILNat 2.1 VSG gene.

Genes encoding various Trypanosoma (Trypanozoon) brucei variable surface glycoproteins (VSGs) show considerable conservation among different members of this species, known as isotypes. The occurrence of isotypes in other salivarian trypanosomes has not been well documented. We have cloned sequences encoding Trypanosoma (Nannomonas) congolense ILNat 2.1 VSG, and used it in DNA blot hybridization analyses of this and other T. congolense clones originating from geographically separate regions of East Africa. The data indicate that the expression of ILNat 2.1 VSG gene proceeds by duplicative transposition resulting in the presence of an extra expression-linked copy in the expressing clones examined. Furthermore the ILNat 2.1 VSG gene sequence is absent or has greatly diverged, in all other T. (N.) congolense clones that belong to different serodemes. This suggests that some T. (N.) congolense VSGs may be limited to their respective antigen repertoires. The data are discussed in the light of their implications for antigenic variation in T. (N.) congolense, and parasite epidemiology.

Africa, Eastern↗
PubMed1985

Putative regulatory sequences for the transcription of mini-exons in Trypanosoma brucei as revealed by S1 sensitivity.

The 35-nucleotide (nt) mini-exon found at the 5' end of most Trypanosoma brucei mRNAs is encoded as part of a tandem 1.35-kb repeat in genomic DNA. We cloned this DNA and identified an S1-sensitive site in supercoiled plasmids containing mini-exon repeats. This site is situated on a poly(dA-dT) stretch that is variable in length in different copies of repeat. Poly(dA-dT) is capable of forming abnormal DNA helix configurations, some of which are induced by supercoiling. The S1 site may have a role in regulation of mini-exon transcription.

Animals↗
PubMed1984

T-cell mediated immunity in murine malaria. I. Induction of T-cell dependent proliferative responses to Plasmodium chabaudi.

To investigate the mechanisms of cell mediated immunity to malaria, we studied different systems to measure specific activation of T lymphocytes by P. chabaudi antigens. Mice were primed by subcutaneous administration of parasite antigens followed by co-cultivation of lymphocytes taken from the draining lymph nodes in the presence of the priming antigen. A marked proliferative response was observed which was shown to be antigen specific, T-cell mediated and accessory cell dependent. Continuous T-cell lines were propagated in culture by repetitive restimulation in the presence of antigen and accessory cells, followed by expansion in a conditioned medium containing T-cell growth factors. These lines could be induced to proliferate to the priming antigen only in the presence of syngeneic accessory cells thus indicating that H-2 restriction operates in the recognition of plasmodium antigens by T cells. We also induced parasite specific T cells by the use of an in vitro primary 'education' system. Lymphocytes from unprimed mice were sensitized on parasite-fed macrophages and were then injected subcutaneously into each hind foot pad of syngeneic animals. This led to recruitment of antigen-reactive cells which were assayed in vitro by the ability of lymphocytes taken from the draining popliteal lymph nodes to proliferate in response to the sensitizing antigen. In vivo immunization with Plasmodium antigen fed macrophages also signalled antigen specific T cells that recruited reactive T cells in the draining lymph nodes.

Animals↗
PubMed1984

T cell-mediated immunity in murine malaria. II. Induction of protective immunity to P. chabaudi by antigen-fed macrophages and antigen-educated lymphocytes.

We previously described assay systems for generating antigen specific proliferating T cells to P. chabaudi antigens. In the present study we examine whether the various sensitization approaches confer immunity against a cloned virulent strain IP-PCI of P. chabaudi. We present data indicating that effective specific protective immunity can be induced through P. chabaudi antigen fed macrophages and antigen educated spleen cells (initiator lymphocytes). The expression of this protective immunity is proposed to depend on (a) antigen presentation and/or accessory function of macrophages and (b) the subsequent activation of T cell functions related to protection. Indeed analysis of different macrophage populations revealed a correlation between the expression of Ia molecules and IL-1 secretion with their capacity to induce antigen specific T cells in vivo and subsequent protective immune mechanisms. Thus these results emphasize the critical functions of accessory cells in determining the outcome of malaria infections.

Animals↗
PubMed1983

The immunomodulatory effect of anti-Micrococcus luteus antibodies. I. Effect on in vitro rabbit T cell functions.

A range of purified rabbit anti-Micrococcus luteus antibodies (anti-MCAb) were tested for their ability to interfere with a variety of in vitro immune responses. Such antibodies strongly inhibited the secondary IgG antibody response to sheep red blood cells without affecting the IgM response or the proliferative responses to mitogens and antigens. By exposing lymphocyte populations to anti-MCAb, it was found that such reagents exerted a strong mitogenic effect on rabbit T lymphocytes, provided these cells were derived from antigen-activated lymph nodes. This mitogenic effect was also obtained with F(ab')2 fragments of anti-MCAb and with hybridoma-derived anti-MCAb. Collectively, these data indicate that anti-MCAb inhibit the initiation of IgG synthesis possibly through the expansion of immunoregulatory T cell subsets.

Animals↗
PubMed1983

Rabbit leukocyte surface antigens defined by monoclonal antibodies.

Several monoclonal antibodies (mAb) against rabbit leukocytes were characterized in binding and functional studies. mAb 1.24 stains thymocytes, bone marrow cells, peripheral T and B cells and blood monocytes. T cells express more 1.24 antigen than B cells. In the absence of added complement (C), mAb 1.24 inhibits alloantigen-, concanavalin A (Con A)-, and phytohemagglutinin (PHA)-, but not pokeweed mitogen (PWM)- or anti-immunoglobulin (Ig)-induced cell proliferation. It also strongly blocks anti-sheep erythrocyte plaque-forming cell responses. A second mAb, designated 4.B9, binds to 20% of thymocytes and to most, if not all, peripheral T cells and in vitro-activated T cell blasts. A third one, 10.B3, is reactive with the nearly entire thymocyte and a major peripheral T cell population. Two-color membrane immunofluorescence reveals the presence of a small population of peripheral blood leukocytes which bear surface Ig and are weakly stained by mAb 4.B9 and 10.B3. Without C, both 4.B9 and 10.B3 inhibit Con A- and PHA-induced mitogenesis, but have no effect on PWM-, antigen-, or alloantigen-induced cell proliferation. Depletion of 4.B9+ cells by panning or complement lysis completely abrogates proliferative responsiveness to antigen and alloantigen, significantly reduces responsiveness to the T cell mitogens Con A and PHA, but enhances that to the B cell mitogen anti-Ig. A fourth mAb, 12.C7, binds to 60% of thymocytes and to 10-30% of peripheral T lymphocytes at high-level fluorescence. T cell blasts obtained in mixed leukocyte reactions are partially stained by mAb 12.C7, while those obtained after Con A or PHA activation are not. In addition, mAb 12.C7 is completely unreactive with B cells or monocytes. Without complement, it does not seem to interfere with any of the in vitro functions tested. All antigens studied here do not appear to be expressed in nonleukon tissues, as they do not bind to erythrocytes and are absent from brain, heart, liver and kidney as shown by quantitative absorption analysis.

Animals↗
PubMed1983

Gene activation and re-expression of a Trypanosoma brucei variant surface glycoprotein.

The expression of the Trypanosoma brucei variant surface glycoprotein AnTat 1.1 proceeds by a mechanism that transfers a duplicated gene copy into a new genomic environment, the so-called expression site, where it will be expressed. We have isolated a genomic fragment containing the region spanning the expression site-transposon junction, and the 5' half of the coding sequence. Comparing this DNA segment with its template copy (basic copy) allowed us to identify the exact breaking point and indicated a base sequence which could be involved in initiating the transposition event. Sequencing data also indicated that the co-transposed segment 5' to the coding sequence is 430 bp in length. The extreme 5' end of the mRNA is derived from a region in the expression site not immediately adjacent to the transposed DNA segment. This particular sequence exists in multiple copies in the genome and is common to the mRNA of all variant surface glycoproteins so far analysed.

Animals↗
PubMed1983

The quaternary Gs3 and Gs7 allotypes of the rabbit: generation of the determinants by interspecies molecular hybridization.

A number of allotypic markers of the rabbit immunoglobulins are present only on intact immunoglobulin molecules and not on the isolated heavy or light chains. Some of these markers, although determined by the kappa light chain, are limited to a single heavy chain class of Ig. They can be generated by in vitro hybridization of the kappa light chain with the appropriate heavy chain. The quaternary IgG allotypic determinants Gs3 and Gs7 which are determined respectively by the b4.1 and b4.2 allelic variants of the kappa b4 light chain can be generated not only by in vitro hybridization of these light chains with a rabbit gamma chain, but also to a certain extent by their hybridization to gamma chains derived from other species.

Animals↗
PubMed1982

Production of IgG-specific auto-anti-allotypes in b4.2-suppressed rabbits.

Rabbits were completely suppressed for kappa chain allotype b4.2, and autoantibodies against b4.1 or b4.2 could be raised in 2 out of 3 animals. The animal immunized with b4.1 produced anti-b4 and anti-Ms3, two activities which have never as yet been found together in one antiserum. Both autoantisera lacked the capacity to bind b4.2-IgM, whereas they precipitated 4.2-IgG very well. In one animal, anti-b4 IgM activity appeared after the sixth immunization, at the age of 14 months. Allotype suppression was maintained in both rabbits till the end of their lives whereas all control animals recovered within 6 months. The autoantisera which were specific for b4 IgG could not induce suppression in vivo. However, specific inhibition of b4 IgG secretion was observed in vitro.

Animals↗