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S Shivakumar

Publications and source records attributed to S Shivakumar.

At least 37 records · Page 2Linked to original sources
PubMed1993

Two wnt genes in Caenorhabditis elegans.

wnt genes encode secretory glycoproteins that have been implicated in growth control and development in mice, frogs and insects. In this report we examine properties of two wnt genes recently identified in the nematode Caenorhabditis elegans. The first gene, Ce-wnt-1, was previously identified by a polymerase chain reaction-based screen of genomic DNA, and the second, Ce-wnt-2, was fortuitously encountered in a survey of clones in a cDNA library by the Caenorhabditis Genome Project. Full-length or nearly full-length cDNAs representing both mRNAs encode proteins that are similar in length, sequence and functional domains to other Wnt proteins. Primary products of 372 and 362 amino acids begin with a hydrophobic signal peptide, include two potential N-linked glycosylation sites and contain the 22 cysteine residues conserved throughout the wnt family. In contrast to mammalian and insect wnt genes with four or five exons and conserved intron-exon boundaries, Ce-wnt-1 has nine coding exons; only one of the eight identified introns interrupts the coding sequence at a position homologous to an intron position in other wnt genes. The major transcript derived from Ce-wnt-1 is 1.4 kb in length, and the 22 nucleotides at its 5' end are added by a trans-splicing mechanism. Ce-wnt-2 is also expressed via a single major transcript, 1.5 kb in length. Both RNAs are detectable in all larval forms and adults, but they are most abundant at the embryonic stage. Ce-wnt-1 is localized to the left arm of chromosome II and Ce-wnt-2 maps to a cluster of genes on chromosome IV.

Amino Acid Sequence↗
PubMed1989

T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis.

It is generally accepted that human Th cells express the surface glycoproteins CD4 and alpha/beta-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and alpha/beta TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the gamma/delta TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and alpha/beta TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic variety of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, alpha/beta TCR+ or CD4-/CD8-, alpha/beta TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies.

Adult↗
PubMed1989

The molecular context of determinants within the priming antigen establishes a hierarchy of T cell induction: T cell specificities induced by peptides of beta-galactosidase vs. the whole antigen.

The antibody response following priming with a macromolecule or a peptide will depend on the regulatory T cells that become activated by the antigenic determinants available. In this report, activation of T helper (Th) and T suppressor (Ts) cells by determinants on beta-galactosidase (GZ) was examined by comparing native GZ [1023 amino acid (a.a.) residues per monomer] with peptides from the immunodominant region encompassing residues 3 to 187. Each immunogen established its characteristic hierarchy of dominance of determinants within it: in particular, GZ and CB-2-3 (a.a. 3-187) each induced immunodominant Th cells which could not be induced by T8 (a.a. 60-140). Hierarchies of suppressor determinant are also created: T8-Ts suppresses all Th specificities and therefore can be deemed immunodominant: T8-2-Ts and T8-3-Ts have a more selective suppressor activity and can be considered subdominant. We conclude that the outcome of immunization shifts with a change in the nature of the immunogen and the context within which the determinant lies will crucially influence its expression. A particular "context" presumably determines the likely order of processing of that molecule which leads to a characteristic relationship among the Ts, Th and B cell determinants involved.

Animals↗
PubMed1988

Selective expression of the Ly-6C.2 epitope on Lyt-2+ T cells that can develop in the absence of thymic influence.

The present study focused on attempts to correlate the expression of T cell differentiation antigens and development. A series of mAb was developed that recognized an Ly-6.2-linked Ag, Ly-6C.2. These mAb reacted with a subset of peripheral Lyt-2+ T lymphocytes but not Lyt-2+ thymocytes. Functional analysis of the Lyt-2+, Ly-6C.2- and Lyt-2+, Ly-6C.2+ subsets demonstrated that both cell types responded in class I and class II allogeneic MLC as well as in virus-specific cell-mediated cytolysis assay, although precursor frequency analysis suggested that the majority of precursor CTL were Ly-6C.2+. The marker did not appear to represent an activation Ag because Ly-6C.2-, Lyt-2+ precursor CTL generated Ly-6C.2-, Lyt-2+ CTL. Finally, virtually all splenic Lyt-2+ T cells from athymic (nu/nu) mice were Ly-6C.2+ whereas all thymic CTL were Ly-6C.2-. These results suggested that Ly-6C.2+, Lyt-2+ T cells may represent a distinct lineage of Lyt-2+ T cells that can develop in the absence of thymic influence.

Animals↗
PubMed1988

Specific binding of human plasma high density lipoprotein (cruzin) to Trypanosoma cruzi.

Binding of high density lipoprotein (HDL) to Trypanosoma cruzi was examined because of its ability to specifically inhibit the parasite's neuraminidase. 125I-Labeled HDL bound to live and glutaraldehyde-fixed parasites equally well either at 37 degrees C or at 4 degrees C. Binding was saturable and inhibited by unlabeled HDL but not by unrelated plasma proteins. Specificity of the T. cruzi-HDL interaction was confirmed using fluorescein labeled HDL which bound to T. cruzi but not to T. rangeli, a species whose neuraminidase is not inhibited by HDL. Binding of HDL to T. cruzi paralleled the neuraminidase activity exhibited by the parasite's different stages and strains. In agreement with this finding, Steck and Wallach analysis of the binding data showed that the number of HDL binding sites was greater in infective trypomastigotes and on strains with high neuraminidase activity. However, the association constant of the binding did not change within the various developmental forms and strains of T. cruzi, suggesting that HDL bound to the same receptor, presumably having neuraminidase activity.

Animals↗