Inhibition of the catalytic activity of human transaldolase by antibodies and site‐directed mutagenesis

Bánki, Katalin; Perl, András

doi:10.1016/0014-5793(95)01446-2

Cited by 27 publications

(26 citation statements)

References 26 publications

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“…Catalytic activity of rTAL-H was also inhibited in the presence of purified Igs from MS patients ALV and LAK. These data demonstrated that high affinity autoantibodies from patients with MS recognized not only the immunoblotted fulllength TAL-H protein and its NH 2 -terminal fragment (16) but functionally relevant COOH-terminal epitopes as well (38). The presence of autoantibodies to multiple TAL-H epitopes and the enzyme inhibitory capacity of a subset of autoantibodies suggests that the intact TAL-H protein has become the source of antigenic drive in these patients.…”

Section: Discussionmentioning

confidence: 88%

Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.

Colombo¹,

Bánki²,

Tatum³

et al. 1997

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 88%

Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.

Colombo¹,

Bánki²,

Tatum³

et al. 1997

J. Clin. Invest.

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“…Patients with MS have TAL Abs in their blood and cerebrospinal fluid (21)(22)(23)(24)(25)(26)(27)(28)(29). TAL autoantibodies recognize immunoblotted and three-dimensional epitopes and inhibit enzymatic activity of TAL (36). By constrast, TAL Abs were absent in normal individuals and patients with other autoimmune and neurological diseases (21) and, under identical conditions, no MBP Abs were found in serum and cerebrospinal fluid of MS patients (29).…”

Section: Ultiple Sclerosis (Ms)mentioning

confidence: 99%

CD8+ T Cell-Mediated HLA-A*0201-Restricted Cytotoxicity to Transaldolase Peptide 168–176 in Patients with Multiple Sclerosis

Niland

Bánki²,

Biddison

et al. 2005

The Journal of Immunology

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Transaldolase (TAL) is expressed at selectively high levels in oligodendrocytes and targeted by autoreactive T cells of patients with multiple sclerosis (MS). Among 14 TAL peptides with predicted HLA-A2 binding, TAL 168–176 (LLFSFAQAV, TALpep) exhibited high affinity for HLA-A2. Prevalence of HLA-A2-restricted CD8+ T cells specific for TALpep was increased in PBMC of HLA-A2+ MS patients, as compared with HLA-A2− MS patients, HLA-A2+ other neurological disease patients, and HLA-A2+ healthy donors. HLA-A*0201/TALpep tetramers detected increased frequency of TAL-specific CD8+ T cells, and precursor frequency of TAL-specific IFN-γ-producing T cells was increased in each of seven HLA-A2+ MS patients tested. Stimulation by TALpep or rTAL of PBMC from HLA-A2+ MS patients elicited killing of TALpep-pulsed HLA-A2-transfected HmyA2.1 lymphoma cells, but not HLA-A3-transfected control HmyA3.1 targets. Without peptide pulsing of targets, HLA-A2-transfected, but not control MO3.13 oligodendroglial cells, expressing high levels of endogenous TAL, were also killed by CD8+ CTL of MS patients, indicating recognition of endogenously processed TAL. TCR Vβ repertoire analysis revealed use of the TCR Vβ14 gene by T cell lines (TCL) of MS patients generated via stimulation by TAL- or TALpep-pulsed APCs. All TAL-specific TCL-binding HLA-A*0201/TALpep tetramers expressed TCR Vβ14 on the cell surface. Moreover, Ab to TCR Vβ14 abrogated cytotoxicity by HLA-A2-restricted TAL-specific TCL. Therefore, TAL-specific CTL may serve as a novel target for therapeutic intervention in patients with MS.

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“…7A, which is published as supporting information on the PNAS web site). This manipulation deleted amino acid residues 138-153, including lysine 142, which is essential for catalytic activity of TAL (11). The 129SvJ-derived TC1 ES cells heterozygous for the disrupted allele were microinjected into C57BL͞6 blastocysts to generate chimeras.…”

Section: Inactivation Of the Mouse Tal (Tal-m) Gene Locus By Homologousmentioning

confidence: 99%

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

Perl

Qian²,

Chohan³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Fertility of spermatozoa depends on maintenance of the mitochondrial transmembrane potential (⌬ m), which is generated by the electron-transport chain and regulated by an oxidation-reduction equilibrium of reactive oxygen intermediates, pyridine nucleotides, and glutathione (GSH). Here, we report that male mice lacking transaldolase (TAL) ؊/؊ are sterile because of defective forward motility. TAL ؊/؊ spermatozoa show loss of ⌬m and mitochondrial membrane integrity because of diminished NADPH, NADH, and GSH. Mitochondria constitute major Ca 2؉ stores; thus, diminished mitochondrial mass accounts for reduced Ca 2؉ fluxing, defective forward motility, and infertility. Reduced forward progression of TAL-deficient spermatozoa is associated with diminished mitochondrial reactive oxygen intermediate production and Ca 2؉ levels, intracellular acidosis, and compensatory down-regulation of carbonic anhydrase IV and overexpression of CD38 and ␥-glutamyl transferase. Microarray analyses of gene expression in the testis, caput, and cauda epididymidis of TAL ؉/؉ , TAL ؉/؊ , and TAL ؊/؊ littermates confirmed a dominant impact of TAL deficiency on late stages of sperm-cell development, affecting the electrontransport chain and GSH metabolism. Stimulation of de novo GSH synthesis by oral N-acetyl-cysteine normalized the low fertility rate of TAL ؉/؊ males without affecting the sterility of TAL ؊/؊ males. Whereas TAL ؊/؊ sperm failed to fertilize TAL ؉/؉ oocytes in vitro, sterility of TAL ؊/؊ sperm was circumvented by intracytoplasmic sperm injection, indicating that TAL deficiency influenced the structure and function of mitochondria without compromising the nucleus and DNA integrity. Collectively, these data reveal an essential role of TAL in sperm-cell mitochondrial function and, thus, male fertility. F orward motility and fertility of spermatozoa depend on production of reactive oxygen intermediates (ROIs) (1) and maintenance of the mitochondrial transmembrane potential (⌬ m ) (2, 3). ⌬ m is generated by the electron-transport chain and subject to regulation by an oxidation-reduction equilibrium of ROI, pyridine nucleotides (NADH͞NAD ϩ NADPH͞NADP), and reduced glutathione (GSH) (4). In turn, NADPH, a reducing equivalent required for biosynthetic reactions and regeneration of GSH from its oxidized form, is produced by the pentose phosphate pathway (PPP) (5). The PPP was originally formulated based on metabolites and enzymes detected in yeast (6). Thus, PPP comprises two separate oxidative and nonoxidative phases. Enzymes of the oxidative phase, glucose 6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase, can generate both ribose 5-phosphate (R5P) and NADPH. Although enzymes of the nonoxidative phase, transketolase (TK) and transaldolase (TAL), can convert R5P into glucose 6-phosphate (G6P) for the oxidative phase, and, thus, indirectly, these enzymes can also contribute to the generation of NADPH, the significance of the nonoxidative branch is less well established. Certain organisms (7,8) and mammalian tissu...

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Inhibition of the catalytic activity of human transaldolase by antibodies and site‐directed mutagenesis

Cited by 27 publications

References 26 publications

Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.

Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.

CD8+ T Cell-Mediated HLA-A*0201-Restricted Cytotoxicity to Transaldolase Peptide 168–176 in Patients with Multiple Sclerosis

Transaldolase is essential for maintenance of the mitochondrial transmembrane potential and fertility of spermatozoa

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