ABSTRACT CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) mem... more ABSTRACT CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) member comprising one variable and one constant C2-type Igsf domain, a transmembrane segment and a cytoplasmic tail. Although resembling that of the TCR and immunoglobulins, the variable domain is not encoded by somatic rearrangement of the gene but by splicing of two half-domain exons. The C2 domain, also encoded by two exons, has an extra pair of cysteines. The transmembrane segment is free of charged residues, and the cytoplasmic tail (70 amino acids) contains one tyrosine and many glutamic acid residues. ChT1, a chicken homologue of CTX, has the same structural and genetic features, and both molecules are expressed on the thymocyte surface. We cloned new mouse (CTM) and human (CTH) cDNA and genes which are highly homologous to CTX/ChT1 but not lymphocyte specific. Similarity with recently described human cell surface molecules, A33 antigen and CAR (coxsackie and adenovirus 5 receptor), and a number of expressed sequence tags leads us to propose that CTX defines a novel subset of the Igsf, conserved throughout vertebrates and extending beyond the immune system. Strong homologies within vertebrate sequences suggest that the V and C2 CTX domains are scions of a very ancient lineage.
Having read Chaps. 3 and 4, one might well be forgiven for assuming that pathogens should have lo... more Having read Chaps. 3 and 4, one might well be forgiven for assuming that pathogens should have long since ceased to be a problem. After all, immune receptor repertoires have been selected to “see” all sorts of different pathogens, and the information they generate can activate powerful effector mechanisms that should certainly be able to destroy all intruders. But we all know that this is not the case, and the reason is that, host–pathogen interactions are always an arms race (see Sect. 1.9), and so any effective defensive move made by the host merely provides the selection pressure that drives the evolution of new virulence strategies in pathogens. And indeed, random mutation and selection have provided pathogens with all sorts of ways to evade immune system receptors, to interfere with the subsequent signal transduction pathways, and to escape from terminal effector systems such as complement, granulocytes and CD8+ T-killer cells. In its turn, every new pathogen virulence strategy drives the selection of new host resistance mechanisms. It is a never-ending struggle in which sometimes the pathogen, and then sometimes the host, manages to achieve a short-lived advantage.
Complement component C3 synthesis by two human lymphoid cell lines was investigated at the mRNA a... more Complement component C3 synthesis by two human lymphoid cell lines was investigated at the mRNA and protein levels. We report that the C3 gene is constitutively transcribed and that C3 protein is synthesized, secreted and proteolytically processed in cell lines of the lymphoid lineage. Because C3 fragments are implicated in lymphocyte growth control, we will also discuss the significance of C3 fragments as potential autocrine growth regulators.
The rare Xenopus gilli is restricted to the southern tip of South Africa where it occurs sympatri... more The rare Xenopus gilli is restricted to the southern tip of South Africa where it occurs sympatrically with the much more numerous Xenopus laevis laevis. Specimens of intermediate phenotype are occasionally found on the Cape Flats, and a sample of these was examined for evidence of hybridization. Serological, immunological and reproductive studies showed that one female was an F1 hybrid between X. gilli and X. I. laevis; a second female, which exhibited one X. gilli specific serum protein amongst otherwise laevis characters, demonstrated introgression of gilli genes into the laevis species. Cross‐breeding between the two sympatric Xenopus species represents a danger for the survival of the already‐vulnerable X. gilli. The genetic behaviour of hybrids also carries implications of evolutionary potential, on the one hand creating gene flow between species, and on the other hand capable of generating new polyploid hybrid species. There is evidence that allopolyploidy has been an important process in the evolution of Xenopus.
Nuclear transplantation experiments show that differentiated cells, such as lymphocytes, from the... more Nuclear transplantation experiments show that differentiated cells, such as lymphocytes, from the adult frog can express the genes necessary for tadpole development. The transplanted cells were proven to be lymphocytes by immunological methods. The origin of the tadpoles that developed after lymphocyte nuclei injections was ascertained by a karyotypic marker.
Determining the relative importance of the elements of the immune sytem is a major task to which ... more Determining the relative importance of the elements of the immune sytem is a major task to which comparative studies may help first in pointing to key elements and second in suggesting their phylogenetic origin. These comparative analyses are complicated by many difficulties due to the following facts. 1) The immune system coevolved with the other physiological systems of the organism and its evolution should not be considered as the evolution of a single independent entity. 2) With respect to the history of the system one has a very incomplete and perhaps misleading view of the phylogeny of the Animal Kingdom. 3) The immune system with what we know of its genetic multiplicity is going to be a complex evolving unit with probably an enormous amount of flexibility enabling some of its elements to evolve in a few generations perhaps as fast as in the history of the species, not to mention its somatic evolution during ontogeny.
Cold Spring Harbor Symposia on Quantitative Biology, 1977
... Antibody Synthesis in Genetically Identical Frogs Totally identical frogs can be obtained by ... more ... Antibody Synthesis in Genetically Identical Frogs Totally identical frogs can be obtained by induc-ing the gynogenic development of identical diploid eggs produced by certain female hybrids of Xenopus (X. laevis X. gilli) (Kobel and Du Pasquier 1975). ...
Current Topics in Microbiology and Immunology, 1998
The antibody responses of ectothermic (cold blooded) vertebrates do not mature in the same fashio... more The antibody responses of ectothermic (cold blooded) vertebrates do not mature in the same fashion as responses analyzed in mice. This has been demonstrated by either a total lack of affinity maturation in some species or a much lower rise in affinity in others (reviewed in Du Pasquier 1993). When it was determined that all ectotherms studied possess large numbers of V(D)J genes, and that rearrangement processes to establish Ig repertoires are essentially the same as those in mouse and human, it was theorized that poor immune responses in ectotherms could be explained by a suboptimal utilization of somatic mutants (Du Pasquier 1982, 1993). Another interpretation was that somatic mutation in the immune system arose late in vertebrate evolution, after emergence of the rearrangement process that generates functional V genes (Matsunaga 1985). Recent studies in cartilaginous fish (horned shark and nurse shark) and an amphibian (Xenopus) have shown conclusively that in addition to all of the molecular building blocks of the adaptive immune system, somatic hypermutation in immune-related genes is present in all jawed vertebrates. In this chapter we review the evidence for mutation in ectotherms, debate its importance to the immune system of these creatures, and speculate on its origins.
ABSTRACT CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) mem... more ABSTRACT CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) member comprising one variable and one constant C2-type Igsf domain, a transmembrane segment and a cytoplasmic tail. Although resembling that of the TCR and immunoglobulins, the variable domain is not encoded by somatic rearrangement of the gene but by splicing of two half-domain exons. The C2 domain, also encoded by two exons, has an extra pair of cysteines. The transmembrane segment is free of charged residues, and the cytoplasmic tail (70 amino acids) contains one tyrosine and many glutamic acid residues. ChT1, a chicken homologue of CTX, has the same structural and genetic features, and both molecules are expressed on the thymocyte surface. We cloned new mouse (CTM) and human (CTH) cDNA and genes which are highly homologous to CTX/ChT1 but not lymphocyte specific. Similarity with recently described human cell surface molecules, A33 antigen and CAR (coxsackie and adenovirus 5 receptor), and a number of expressed sequence tags leads us to propose that CTX defines a novel subset of the Igsf, conserved throughout vertebrates and extending beyond the immune system. Strong homologies within vertebrate sequences suggest that the V and C2 CTX domains are scions of a very ancient lineage.
Having read Chaps. 3 and 4, one might well be forgiven for assuming that pathogens should have lo... more Having read Chaps. 3 and 4, one might well be forgiven for assuming that pathogens should have long since ceased to be a problem. After all, immune receptor repertoires have been selected to “see” all sorts of different pathogens, and the information they generate can activate powerful effector mechanisms that should certainly be able to destroy all intruders. But we all know that this is not the case, and the reason is that, host–pathogen interactions are always an arms race (see Sect. 1.9), and so any effective defensive move made by the host merely provides the selection pressure that drives the evolution of new virulence strategies in pathogens. And indeed, random mutation and selection have provided pathogens with all sorts of ways to evade immune system receptors, to interfere with the subsequent signal transduction pathways, and to escape from terminal effector systems such as complement, granulocytes and CD8+ T-killer cells. In its turn, every new pathogen virulence strategy drives the selection of new host resistance mechanisms. It is a never-ending struggle in which sometimes the pathogen, and then sometimes the host, manages to achieve a short-lived advantage.
Complement component C3 synthesis by two human lymphoid cell lines was investigated at the mRNA a... more Complement component C3 synthesis by two human lymphoid cell lines was investigated at the mRNA and protein levels. We report that the C3 gene is constitutively transcribed and that C3 protein is synthesized, secreted and proteolytically processed in cell lines of the lymphoid lineage. Because C3 fragments are implicated in lymphocyte growth control, we will also discuss the significance of C3 fragments as potential autocrine growth regulators.
The rare Xenopus gilli is restricted to the southern tip of South Africa where it occurs sympatri... more The rare Xenopus gilli is restricted to the southern tip of South Africa where it occurs sympatrically with the much more numerous Xenopus laevis laevis. Specimens of intermediate phenotype are occasionally found on the Cape Flats, and a sample of these was examined for evidence of hybridization. Serological, immunological and reproductive studies showed that one female was an F1 hybrid between X. gilli and X. I. laevis; a second female, which exhibited one X. gilli specific serum protein amongst otherwise laevis characters, demonstrated introgression of gilli genes into the laevis species. Cross‐breeding between the two sympatric Xenopus species represents a danger for the survival of the already‐vulnerable X. gilli. The genetic behaviour of hybrids also carries implications of evolutionary potential, on the one hand creating gene flow between species, and on the other hand capable of generating new polyploid hybrid species. There is evidence that allopolyploidy has been an important process in the evolution of Xenopus.
Nuclear transplantation experiments show that differentiated cells, such as lymphocytes, from the... more Nuclear transplantation experiments show that differentiated cells, such as lymphocytes, from the adult frog can express the genes necessary for tadpole development. The transplanted cells were proven to be lymphocytes by immunological methods. The origin of the tadpoles that developed after lymphocyte nuclei injections was ascertained by a karyotypic marker.
Determining the relative importance of the elements of the immune sytem is a major task to which ... more Determining the relative importance of the elements of the immune sytem is a major task to which comparative studies may help first in pointing to key elements and second in suggesting their phylogenetic origin. These comparative analyses are complicated by many difficulties due to the following facts. 1) The immune system coevolved with the other physiological systems of the organism and its evolution should not be considered as the evolution of a single independent entity. 2) With respect to the history of the system one has a very incomplete and perhaps misleading view of the phylogeny of the Animal Kingdom. 3) The immune system with what we know of its genetic multiplicity is going to be a complex evolving unit with probably an enormous amount of flexibility enabling some of its elements to evolve in a few generations perhaps as fast as in the history of the species, not to mention its somatic evolution during ontogeny.
Cold Spring Harbor Symposia on Quantitative Biology, 1977
... Antibody Synthesis in Genetically Identical Frogs Totally identical frogs can be obtained by ... more ... Antibody Synthesis in Genetically Identical Frogs Totally identical frogs can be obtained by induc-ing the gynogenic development of identical diploid eggs produced by certain female hybrids of Xenopus (X. laevis X. gilli) (Kobel and Du Pasquier 1975). ...
Current Topics in Microbiology and Immunology, 1998
The antibody responses of ectothermic (cold blooded) vertebrates do not mature in the same fashio... more The antibody responses of ectothermic (cold blooded) vertebrates do not mature in the same fashion as responses analyzed in mice. This has been demonstrated by either a total lack of affinity maturation in some species or a much lower rise in affinity in others (reviewed in Du Pasquier 1993). When it was determined that all ectotherms studied possess large numbers of V(D)J genes, and that rearrangement processes to establish Ig repertoires are essentially the same as those in mouse and human, it was theorized that poor immune responses in ectotherms could be explained by a suboptimal utilization of somatic mutants (Du Pasquier 1982, 1993). Another interpretation was that somatic mutation in the immune system arose late in vertebrate evolution, after emergence of the rearrangement process that generates functional V genes (Matsunaga 1985). Recent studies in cartilaginous fish (horned shark and nurse shark) and an amphibian (Xenopus) have shown conclusively that in addition to all of the molecular building blocks of the adaptive immune system, somatic hypermutation in immune-related genes is present in all jawed vertebrates. In this chapter we review the evidence for mutation in ectotherms, debate its importance to the immune system of these creatures, and speculate on its origins.
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