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Y Tikochinski

Publications and source records attributed to Y Tikochinski.

6 recordsLinked to original sources
PubMed1999

A shared TCR CDR3 sequence in NOD mouse autoimmune diabetes.

T cells involved in autoimmune diseases have been characterized by the genetic elements used to construct their autoimmune TCR. In the present study, we sequenced the alpha and beta chains of the TCR expressed by a CD4(+) T cell clone, C9, functional in NOD mouse diabetes. Clone C9 can adoptively transfer diabetes or, when attenuated, C9 can be used to vaccinate NOD mice against diabetes. Clone C9 recognizes a peptide epitope (p277) of the 60 kDa heat shock protein (hsp60) molecule. We now report that the C9 TCR beta chain features a CDR3 peptide sequence that is prevalent among NOD mice. This CDR3 element is detectable by 2 weeks of age in the thymus, and later in the spleen and in the autoimmune insulitis. Thus, a TCR CDR3beta sequence appears to be a common idiotope associated with mouse diabetes.

Amino Acid Sequence↗
PubMed1999

Regulation of NOD mouse autoimmune diabetes by T cells that recognize a TCR CDR3 peptide.

NOD mice spontaneously develop type I diabetes resulting from autoimmune destruction of their insulin-producing beta cells. Among the self-antigens targeted by NOD autoimmune T cells is a peptide, p277, from the sequence of the 60 kDa heat shock protein (hsp60). Common to the anti-p277 T cell populations of NOD mice is an idiotope, C9, that spans the CDR3 region of the C9 TCR. We now report: (i) that the C9 idiotope peptide can be presented directly to anti-C9 anti-idiotypic T cells by C9 T cells, (ii) that spontaneous anti-C9 anti-idiotypic T cell activity falls as disease progresses, but immunization can activate the anti-idiotypic T cells to regulate the autoimmune process, (iii) that the anti-idiotypic T cells secrete IFN-gamma, but appear to control the disease by down-regulating the IFN-gamma produced by the pathogenic population of anti-p277 T cells, (iv) that intrathymic administration of the C9 idiotope peptide at 1 week of age can accelerate the disease, and (v) that administering the p277 target peptide can up-regulate the anti-idiotypic T cells and arrest the disease process. Thus, the development of NOD diabetes can be regulated by a balance between anti-idiotypic and anti-target peptide autoimmunity, and anti-idiotypic regulation can lead to changes in the cytokine secretion of the autoimmune T cells involved in the disease process.

Amino Acid Sequence↗
PubMed1991

mtDNA polymorphism in two communities of Jews.

Twenty-one types of mtDNA were found in a survey of 39 Israeli Jews, of whom 18 were Sephardic and 21 Ashkenazic. The survey was made with six restriction enzymes that together recognize an average of 600 bp/genome. The differences among the types appear to be due to base substitution at 19 cleavage sites, one deletion, and one conformational mutation. The numbers of differences imply that these modern Jews stem from a minimum of 21 maternal lineages that were already distinct from one another 4,000-5,000 years ago. In three of the four cases where a type was found in more than one person, it occurred in both Ashkenazic and Sephardic populations. The diversity of types in the combined sample of two Jewish populations is lower than both that in a sample from various parts of Africa and that in a sample from various parts of East Asia. Nevertheless, it is as high as that in a sample from diverse parts of New Guinea, an area much larger than that in Israel to which the Jewish population traces back.

Base Composition↗
PubMed1990

(TG)n uncovers a sex-specific hybridization pattern in cattle.

Screening of a bovine genomic library with the human minisatellite 33.6 probe uncovered a family of clones that, when used to probe Southern blots of bovine genomic DNA digested with the restriction enzyme HaeIII or MboI, revealed sexually dimorphic, but otherwise virtually monomorphic, patterns among the larger DNA fragments to which they hybridized. Characterization of one of these clones revealed that it contains different minisatellite sequences. The sexual dimorphism hybridization pattern observed with this clone was found to be due to multiple copies of two tandemly interspersed repeats: the simple sequence (TG)n and a previously undescribed 29-bp sequence. Both repeats appear to share many genomic loci including autosomal loci. In contrast, Southern analysis of AluI- or HinfI-digested bovine DNA with the (TG)n repeat used as a probe yielded substantial polymorphism. These results show that (i) different minisatellites can be found in a cluster, (ii) both simple and more complex repeated sequences other than the simple quaternary (GATA)n repeat can be sexually dimorphic, and (iii) simple repeats can reveal substantial polymorphism.

Animals↗
PubMed1989

Isodisomy of chromosome 7 in a patient with cystic fibrosis: could uniparental disomy be common in humans?

Maternal isodisomy for chromosome 7 was observed in a 4-year-old cystic fibrosis patient with very short stature. In an examination of 11 DNA polymorphisms spanning the entire length of chromosome 7, no paternal contribution could be shown in seven informative loci. Paternity was examined with probes for five polymorphic loci on the Y chromosome, for the pseudo beta-globin locus on chromosome 11 and by Jeffreys's hypervariable probes. The results with the latter gave a probability of 3.7 x 10(-9) for nonpaternity. Chromosomal examination revealed a centromeric heteromorphism of chromosome 7 in the mother, for which the proband was homozygous. Isodisomy of the patient was thus shown for the entire length of a maternal chromosome 7. The mechanisms leading to this isodisomy involve at least two events of abnormal cell division, events that may be meiotic, postzygotic, or both. This proband is the second reported maternal isodisomy; both were detected through homozygosity for CF. Both patients had short stature, which could have been caused by parental imprinting, since similar results have been observed in isodisomic mice. Homozygosity due to uniparental descent in man should be kept in mind as a mechanism for recessive disorders, especially for chromosome 7.

Child, Preschool↗