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1.
The percentages of the -chain variant Hb G-Philadelphia (Hb G) or 2 68 AsnLys2 were evaluated in 84 adult and 18 newborn heterozygotes. These included members of three families who were studied in more detail by nucleic acid hybridization techniques. The adult heterozygotes fell in two categories, one with a higher proportion of Hb G [46.5±1.0% (SD), N=21] and another with lower values (33.9±3.4%, N=63). Among the newborn heterozygotes, two babies fell in the category with the higher proportion of Hb G while 16 babies gave values between 25 and 34%. Studies of -chain gene organization on the parents of one neonate with a Hb G level of 27% at birth and 37% at 8 months excluded the presence of chromosomes with triplicated -chain genes which could lead to the 0G/ genotype. Rather, these studies on five Hb G heterozygotes from three families confirmed the linkage between Hb G and a specific type of -thalassemia-2 associated with the presence of a 16-kbp Bgl II fragment which most probably carries the G locus since it has been found in 19 Hb G heterozygotes studied to date. The presence of an -thal-2 heterozygosity and three -chain genes (0G/) was confirmed among Hb G heterozygotes with lower proportions of this variant. It is likely that the even lower values found in some newborn could arise through defective assembly of G- dimers. The presence of an -thal-2 homozygosity and two active -chain genes, one on each chromosome (0G/0), was confirmed among heterozygotes with the higher proportion of Hb G. One of each of these categories was present in each of the three families investigated. This type of variability in the number of active -chain genes due to a heterozygosity or a homozygosity for -thalassemia-2 explains the trimodality of Hb S percentages among heterozygotes and the atypical hematological or biosynthetic features among patients with -thalassemia and sickle-cell syndromes.This research was supported by USPHS Research Grants HLB-05168 and HLB-15158 and by designated research funds of the Veterans Administration. This is Contribution No. 0693 of the Department of Cell and Molecular Biology, Medical College of Georgia, Augusta. 相似文献
2.
Summary -chains were isolated from two individuals heterozygous for the -chain mutant haptoglobin Marburg. Total amino acid composition and tryptic peptides were compared with -chains from common haptoglobin types. Mb chain preparations are characterized by the presence of -chains with an atypical electrophoretic migration rate and by at least three, possibly four additional peptides in their tryptic digests. It is probable that haptoglobin Marburg is the result of an mutational event other than a single base substitution.Supported by US-PHS grant AM 11796 and by US-PHS grant HD 03321 and aided by a grant from the Deutsche Forschungsgemeinschaft. 相似文献
3.
Ren-Heidenreich L Mordini R Hayman GT Siebenlist R LeFever A 《Cancer immunology, immunotherapy : CII》2002,51(8):417-423
A promising strategy for cancer treatment is adoptive gene therapy/immunotherapy by genetically modifying T cells with a chimeric T cell receptor (cTCR). When transduced T cells (T-bodies) specifically bind to tumor antigens through cTCR, they will become cytotoxic T lymphocytes (CTL) and lyse the tumor cells in a non-major histocompatibility complex (MHC)-restricted manner. Both the FcR gamma-chain and the TCR zeta-chain have been used to construct such cTCR, and both have shown specific cytolytic functions against tumor cells. However, most researchers believe that the zeta-chain generates stronger cytolytic activities against tumor than the gamma-chain and therefore would be a better candidate for cTCR construction. On the other hand, because of the lack of costimulation signaling in such constructs, the T-body might cause activation-induced T cell death (AICD) when bound to tumor antigens. Therefore, one can argue that the gamma-chain might generate less AICD than the zeta-chain because the gamma-chain has only one immunoreceptor tyrosine-based activation motif (ITAM), and the cytolytic activities can be therefore recycled. Two cTCR, GAHgamma and GAHzeta, were constructed and evaluated for cytokine production, specific cytolytic function and AICD in T-bodies after exposure to tumor cells. Using EGP-2-positive LS174T colorectal carcinoma cells as targets, there was no substantial difference observed between a gamma-chain or zeta-chain as the T-body signaling moiety in terms of specific cytolytic functions and induced cytokine production. This paper also demonstrates that, in the absence of a costimulation system, tumor antigen may not trigger apoptosis of T cells transduced with a cTCR carrying either an FcR gamma-chain or a TCR zeta-chain. These observations challenge current ideas about the role of ITAM in T cell activation. 相似文献
4.
Laura M. Garrick Richard L. Sloan Thomas W. Ryan Thomas J. Klonowski Michael D. Garrick 《The Biochemical journal》1978,173(1):321-330
The amino acid sequence of the major β-chain, IIβ, from rat haemoglobins was established with an automated sequencer. Amino acid heterogeneities were found that appear to result from allelic variation at particular residues. We applied several new or unusual techniques in determining the sequence: (1) reaction of the polypeptide with dansylaziridine for detection of cysteine; (2) blockage of the N-terminal residue and the ε-amino group of lysine residues with 1-fluoro-2-nitro-4-trimethylammoniobenzene iodide and subsequent identification of the modified lysine phenylthiohydantoin by absorbance at 420nm; (3) identification of histidine phenylthiohydantoin by its blue fluorescence under long-wave u.v. light; (4) cleavage of the chain into two or three fragments and subsequent sequencing without purification [a detailed statement giving the major phenylthiohydantoins assigned at each step for each sequence run before their alignment in individual sequences has been deposited as Supplementary Publication SUP 50084 (10 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5]; (5) separation of fragments produced by CNBr cleavage by cation-exchange chromatography; (6) peptide sequencing after attachment of the peptide to cytochrome c. The amino acid sequence was confirmed by amino acid compositions of the complete chain, of CNBr fragments 1 and 3, and of 11 purified tryptic peptides. 相似文献
5.
6.
Ren L Yang Z Wang T Sun Y Guo Y Zhang Z Fei J Bao Y Qin T Wang J Huang Y Hu X Zhao Y Li N 《Immunogenetics》2011,63(10):667-678
In humans, classical MHC class II molecules include DQ, DR, and DP, which are similar in structure but consist of distinct α- and β-chains. The genes encoding these molecules are all located in the MHC class II gene region. In non-mammalian vertebrates such as chickens, only a single class II α-chain gene corresponding to the human DRA has been identified. Here, we report a characterization of the duck MHC class II α-chain (Anpl-DRA) encoding gene, which contains four exons encoding a typical signal peptide, a peptide-binding α1 domain, an immunoglobulin-like α2 domain, and Tm/Cyt, respectively. This gene is present in the duck genome as a single copy and is highly expressed in the spleen. Sequencing of cDNA and genomic DNA of the Anpl-DRA of different duck individuals/strains revealed low levels of genetic polymorphism, especially in the same strain, although most duck individuals have two different alleles. Otherwise, we found that the duck gene is located next to class II β genes, which is the same as in humans but different from the situation in chickens. 相似文献
7.
Starch gel electrophoretic and ultracentrifuge methods failed to demonstrate any differences between the hemoglobins of mice of the Shanghai and HBBP/Cag strains and crosses among these strains. The apparent identity of these hemoglobins is thought to stem from the contribution of Asian mice to the British mouse fancy from which the laboratory strains having Hbb-p in part descerd. Maleate buffer of pH 7 or above can be used to prevent the formation of disulfide-bridged dimers of mouse hemoglobins. However, the minor electrophoretic bands of Hbb-p and Hbb-d react with approximately twice as much maleate as the major bands of each of these hemoglobins, although the minor bands like the major contain only one free cysteine group per chain. This can be explained by the alkylation of the -amino of lysine residue 76, but some evidence for the alkylation of histidine in the minor band of Hbb-p is also presented. 相似文献
8.
van Rietschoten JG Smits HH Westland R Verweij CL den Hartog MT Wierenga EA 《Immunogenetics》2000,51(1):30-36
The interleukin-12 receptor (IL-12R) is composed of two subunits, referred to as β1 and β2. Both chains are necessary for
high-affinity IL-12 binding and signalling, although only the IL-12Rβ2 chain contains the intracellular tyrosine residues
responsible for STAT4 activation. This study presents the intron-exon organization of the human IL-12Rβ2-chain gene. Polymerase
chain reaction (PCR) primers designed across the cDNA (U46198) were used to trace introns, by comparing PCR product sizes
obtained using cDNA and genomic DNA as templates. PCR products spanning introns were sequenced to determine the exact splice
sites and flanking regions. The coding region of the gene was found to consist of 15 exons and 14 introns. All intron-exon
boundaries are consistent with the consensus sequence for splice junctions (5′ GT/AG 3′). Comparison of the intron-exon organization
with the human GCSFR gene indicated a remarkably well conserved genomic organization between these two class I cytokine receptors. Interestingly,
we identified an alternatively spliced mRNA, encoding a putative, truncated protein, lacking all signalling potential.
Received: 21 July 1999 / Revised: 2 September 1999 相似文献
9.
Evidence of homology between the β-chain of human haptoglobin and the chymotrypsin family of serine proteases 总被引:2,自引:0,他引:2
Alexander Kurosky Don R. Barnett Marily A. Rasco Tong-Ho Lee Barbara H. Bowman 《Biochemical genetics》1974,11(4):279-293
Amino acid sequences from the β-chain of human haptoglobin are compared with those sequences known for the serine proteases of the chymotrypsin family. In a comparison of some 171 residues of the haptoglobin β-chain (approximately 60% of the protein molecule), approximately 30% of these are identical to residues occurring in sequences of either bovine trypsin, bovine chymotrypsin A, bovine chymotrypsin B, porcine elastase, or bovine thrombin B-chain, and an additional 10% are chemically similar. A combined comparison of the haptoglobin β-chain with the above five serine proteases gave an identity of 56% and a chemical similarity of 11%. Similarity of primary structure is also striking around two of the five half-cystinyl residues so far characterized in long lengths of sequence. These data provide substantial evidence that the β-chain of haptoglobin is homologous to the chymotrypsin family of serine proteases. Proposals are also presented to explain the occurrence of internal homology in the N-terminal region of the β-chain. 相似文献
10.
In a survey of mice from 40 inbred strains, largely previously untested, four alleles were distinguished at the Hba locus, determining structure of adult mouse hemoglobin chain. This finding supports and extends previous sequence studies by others. Methods are given by which each phenotype was characterized by its solubility profile at varying pH and by its chromatography pattern. Concordance was complete between histidine-positive T-4 (defining Hba
c) and high-intermediate solubility profile. In three inbred strains, a distinct new low-solubility profile, not associated with his-positive T-4, was recognized, and mice with this phenotype were classified as Hba
d. Implications of observed widely distributed four-allele polymorphism of mouse hemoglobin -chain structure are discussed.This investigation was supported in part by NIH research grant CA-01074 from the National Cancer Institute and in part by the Virginia and D. K. Ludwig Foundation. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care. 相似文献
11.
Alia Islam Obaid Ullah Beg Bengt Persson Zafar H. Zaidi Hans Jörnvall 《The protein journal》1988,7(5):561-569
The structure of the hernoglobin α-chain of Rose-ringed Parakeet was determined by sequence degradations of the intact subunit, the CNBr fragments, and peptides obtained by digestion with staphylococcal Glu-specific protease and trypsin. Using this analysis, the complete α-chain structure of 21 avian species is known, permitting comparisons of the protein structure and of avian relationships. The structure exhibits differences from previously established avian α-chains at a total of 61 positions, five of which have residues unique to those of the parakeet (Ser-12, Gly-65, Ser-67, Ala-121, and Leu-134). The analysis defines hemoglobin variation within an additional avian order (Psittaciformes), demonstrates distant patterns for evaluation of relationships within other avian orders, and lends support to taxonomic conclusions from molecular data. 相似文献
12.
《Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology》1988,952(3):380-389
With the purpose of establishing whether, as a general rule, regions of a protein chain that are helical in the native structure maintain, at least partially, the same helical structure when isolated in solution, we have prepared the 1–23 fragment of human hemoglobin α-chain, and studied its conformational properties in aqueous solution by CD and1H-NMR. From the analysis of CD and NMR spectral changes with temperature, salt and addition of trifluoroethanol (TFE) it can be concluded that the 1–23 peptide forms a measurable population (18% at 22°C (pH 5.6) TFE/H2O, 30:70 (v/v)) of an α-helix structure that spans the same residues that are helical in the native protein (namely, 6 to 17). These results, taken together with similar ones obtained previously in the 1–19, 21–42 and 50–61 RNAase fragments, support the idea that no helices other than the native ones are actually formed in solution by protein fragments. This implies that the final helical structure of a protein is present from the very beginning of the folding process, and also that such elements of secondary structure can act as primary nucleation centers. 相似文献
13.
Hemoglobin binding with haptoglobin: Delineation of the haptoglobin binding site on the α-chain of human hemoglobin 总被引:3,自引:0,他引:3
Previous studies from this laboratory employing a comprehensive synthetic overlapping peptide strategy showed that the -chain of human hemoglobin (Hb) contains a single haptoglobin (HP) binding region residing within residues 121–135. The present study describes a precise delineation of this Hp-binding site on the -chain. Two overlapping peptides (111–125 and 121–135) spanning this region and a panel of five peptides decreasing at the C-terminal from residue 135 by decrements of two residues (119–135, 119–133, 119–131, 119–129, and 119–127) were synthesized, purified, and characterized. Quantitative radiometric titration of125I-labeled human HP (type 2-1) with adsorbents of each of these synthetic peptides showed that the peptide 119–127 retained a Hp-binding activity equivalent to that of peptide 121–135. This finding indicated that Lys-127 marked the C-terminal boundary of the binding site. Another panel of eight peptides was then synthesized, which had their C-terminus fixed at Lys-127 and increased at the N-terminus by one-residue increments from residue 122 up to residue 115 (122–127, 121–127, 120–127, 119–127, 118–127, 117–127, 116–127, and 115–127). The binding of125I-Hp to adsorbents of these peptides demonstrated that the N-terminal boundary of the site did not extend beyond Valine 121. It is, therefore, concluded that the Hp-binding site on the -chain of human Hb comprises residues 121–127. 相似文献
14.
Summary Collagen from an inferior invertebrate, namely from the sea anemoneActinia equina L., appears to consist of three identical subunits (-chains). New evidence for this situation is reported on the basis of preparative-scale experiments.No fractionation of sea anemone collagen was obtained by CM-cellulose chromatography which is the method of choice for the isolation of vertebrate collagen subunits. On the other hand, the-component (mol. wt., 95.000) could be isolated by gel chromatography. It was homogenous when investigated by polyacrylamide gel electrophoresis (in the presence of sodium dodecyl sulphate) and by ion exchange chromatography on CM-cellulose. The amino acid composition of the-component was identical with that of unfractionated collagen.Divergent evolution of the collagen molecule appears likely since vertebrate collagen molecules are made up of different-chain types. 相似文献
15.
Takamichi Izumi Makoto Kondo Takuya Takahashi Nao Fujieda Atsushi Kondo Naohisa Tamura Tomohiro Murakawa Jun Nakajima Hirokazu Matsushita Kazuhiro Kakimi 《Cytotherapy》2013,15(4):481-491
Background aimsAdoptive immunotherapy is emerging as a potent anti-tumor treatment modality; Vγ9Vδ2 T cells may represent appropriate agents for such cancer immunotherapy. To improve the currently limited success of Vγ9Vδ2 T-cell–based immunotherapy, we examined the in vivo dynamics of these adoptively-transferred cells and hypothesized that interleukin (IL)-15 is the potential factor for Vγ9δ2 T cell in vivo survival.MethodsWe conducted a clinical trial of adoptive Vγ9Vδ2 T-cell transfer therapy in six colorectal cancer patients who received pulmonary metastasectomy. Patients' peripheral blood mononuclear cells were stimulated with zoledronate (5 μmol/L) and IL-2 (1000 IU/mL) for 14 d. Harvested cells, mostly Vγ9Vδ2 T cells, were given intravenously weekly without additional IL-2 eight times in total. The frequency, phenotype and common γ-chain cytokine receptor expression of Vγ9Vδ2 T cells in peripheral blood was monitored by flow cytometry at each time point during treatment and 4 and 12 weeks after the last administration.ResultsAdoptively transferred Vγ9Vδ2 T cells expanded well without exogenous IL-2 administration or lymphodepleting preconditioning. They maintained effector functions in terms of interferon-γ secretion and prompt release of cytotoxic granules in response to PMA/ionomycin or isopentenyl pyrophosphate–positive cells. Because they are IL-2Rα?IL-7Rα?IL-15Rα?IL-2Rβ+γc+, it is likely that IL-2 or IL-15 is required for their maintenance.ConclusionsThe persistence of large numbers of functionally active adoptively transferred Vγ9Vδ2 T cells in the absence of exogenous IL-2 implies that an endogenous factor, such as IL-15 transpresentation, is adequate to support these cells in vivo. 相似文献
16.
Distribution and characterization of a Sandhoff disease-associated 50-kb deletion in the gene encoding the human β-hexosaminidase β-chain 总被引:1,自引:1,他引:0
Hennie Bikker Frank M. van den Berg Ruud A. Wolterman Wim J. Kleijer Jan J. M. de Vijlder Piet A. Bolhuis 《Human genetics》1990,85(3):327-329
Summary A 50-kb deletion was demonstrated in the gene encoding for the -subunit of human hexosaminidase (HEXB), using field inversion gel electrophoresis (FIGE) of SfiI-digested chromosomal DNA from patients with Sandhoff disease. We investigated 14 patients from different parts of Europe and found no deletion in 5 patients, 2 patients homozygous for the deletion, and 7 patients with the deletion in one allele. The distribution of the 50-kb deletion was approximately in agreement with the Hardy-Weinberg equilibrium. The deletion was characterized using chromosomal DNA from one of the two homozygous patients. Restriction fragments were hybridized with a 1.6-kb (almost complete) and a 0.4-kb (5) HEXB cDNA clone. It appeared that the deletion started in intron 5, extending in the 5 direction and causing the loss of exon 1–5 and the promoter area of the HEXB gene. 相似文献
17.
Identical substitution in Hb Ube-1 and Hb K?ln 总被引:1,自引:0,他引:1
18.
A hitherto unknown inherited hemoglobin variant, Hb Tacoma, was discovered in three healthy members of a family of European extraction.Hybridization experiments with canine hemoglobin indicated a structural abnormality in the -chain. The variant was therefore designated as Hb 2 2
Tacoma. Separation of Hb Tacoma from Hb A could only be clearly achieved by starch grain electrophoresis in TEB buffer at pH 8.6–9.0, where Hb Tacoma moved more rapidly towards the anode than Hb A; gradient column chromatography on DEAE cellulose and CM-Sephadex achieved partial separation. The proportion of abnormal hemoglobin in the heterozygote amounted to 43 per cent of the total hemoglobin. Hb Tacoma was less heat resistant and became more rapidly denatured in 8 M urea solution than Hb A, Hb C, or Hb S.On thin-layer starch gel electrophoresis in TCB buffer at pH 8.6 Hb Tacoma was associated with an electrophoretically slow, benzidine-positive component, Hb Tacoma-slow. The exact biochemical nature of this minor component could not be determined, although a polymeric product of Hb Tacoma is suspected.Heterozygosity for Hb Tacoma is associated with a raised Hb A2 level without evidence of -thalassemia.A preliminary report of Hb Tacoma was presented at the Annual Meeting of the American Society of Human Genetics, Boulder, Colorado, August, 1964, and at the Seventh Annual Meeting of the American Society of Hematology, November, 1964, Seattle, Washington (Blood, 24, 848 (1964)). 相似文献
19.
Summary 12 families with Hb 0 Arab from the Burgas district of Bulgaria were examined. Of the 262 members of the 12 families, 44 persons were simple Hb 0 Arab heterozygotes, 18 had -thalassaemia, and 16 were double heterozygotes for Hb 0 Arab and ° thalassaemia. 相似文献