Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By typing a large quantity of family-based material for HLA-B, HLA-DR, C4, C2 and factor B, we were able to derive four-gene complement haplotypes (C4A, C4B, C2, BF) and six-gene MHC haplotypes (HLA-B, complement, HLA-DR). Fourteen six-gene MHC haplotypes showed linkage disequilibrium but exact frequencies could not be determined because it was not always possible to assign null C4 alleles in families where null genes were not clearly seen to segregate. Comparison of unrelated type I diabetes, Graves' disease and Hashimoto's thyroiditis patients with healthy unrelated controls revealed the following MHC allele associations: C4B*3, HLA-DR3 and HLA-DR4 with type I diabetes; BF*F1 and HLA-DR3 with Graves' disease; HLA-DR4 with Hashimoto's thyroiditis. By typing families of type I diabetes and Graves' disease patients we were able to derive two high-risk DR3+ MHC haplotypes for both type I diabetes and Graves' disease. These are HLA-B8 C4A*Q0 C4B*1 BF*S HLA-DR3 and HLA-B18 C4A*3 C4B*Q0 BF*F1 HLA-DR3, and these haplotypes account for most of the associations between these diseases and HLA-DR3. The MHC haplotype HLA-B15 C4A*3 C4B*3 BF*S HLA-DR4 also carries high risk for type I diabetes in this group of patients. Our data suggest that other DR4+ haplotypes, probably containing C4A*3 C4B*1, carry increased risk for type I diabetes whereas haplotypes containing DR4 and C4 C4A*3 C4B*Q0 do not. Our phenotype data suggest that DR4 in Hashimoto's thyroiditis is frequently associated with HLA-B44, C4A*3, C4B*1 and BF*S.
Mol Biol Med 1986 Apr
PMID:Class III alleles and high-risk MHC haplotypes in type I diabetes mellitus, Graves' disease and Hashimoto's thyroiditis. 346 Dec 34

We studied HLA antigen frequency in 54 carefully selected patients with goitrous Hashimoto's thyroiditis. All had an appropriate clinical course, positive family history, antithyroid antibodies and/or a needle biopsy indicating chronic lymphocytic thyroiditis. We found no statistically significant association with any HLA-A, -B, -C or DR specificity.
Mol Biol Med 1986 Apr
PMID:Goitrous Hashimoto's thyroiditis. Lack of association with HLA antigens. 346 Dec 35

Graves' disease is associated with HLA-DR3 in Caucasoids. We have now demonstrated, on the basis of disease-associated MHC haplotypes (A1, Cw3, B8, DR3 and fragments thereof) from 38 families in which more than one member had Graves' disease compared with MHC haplotypes from 56 healthy families, that the risk was highest with the DR locus (relative risk for A1, B8, DR3 = 2.3, for B8, DR3 = 5.3, and for DR3 = 6.8). We further used the sib-pair method to explore linkage of Graves' disease liability to the MHC in 67 affected sib-pairs. The data were consistent with an MHC-linked recessive gene with a frequency of 0.2 to 0.3 and a penetrance of 7.2%; the data, however, accommodated penetrance of up to 16.3%. A recessive model was also consistent with the HLA-B8 genotype distribution in 286 unrelated patients. As the effect of the marker alleles on the course of the disease had been debated several times, we applied a cluster analysis method using 49 clinical and laboratory characteristics, including the HLA-A and HLA-B antigens of 196 patients. Three groups were identified, corresponding to patients with mild disease, Hashitoxicosis and severe (relapsing) disease. The prevalence of HLA-B8 was 8.9%, 21% and 87%, respectively (compared to 18.8% in 380 controls). This suggests the existence of an underlying continuum of genetic liability, apparently related to that for Graves' disease severity, associated with the MHC and mediated through immunoregulatory disturbances.
Mol Biol Med 1986 Feb
PMID:The role of HLA antigens in the manifestation and course of Graves' disease. 348 58

The role of the single carbohydrate moiety present on the HLA-A2 molecule was studied by introducing several amino acid substitutions (by site-directed mutagenesis of the HLA-A2 gene) in the consensus glycosylation sequence Asn-X-Ser. Two different amino acid substitutions of the asparagine residue at position 86 (glutamine and aspartic acid) resulted in the synthesis of ca. 39,000-molecular-weight nonglycosylated heavy chains that were detected in the cytoplasm but not on the surface of mouse L-cell transfectants. However, a low level of surface expression was detected following transfection of human (rhabdomyosarcoma) cells or mouse L cells containing human beta 2-microglobulin. The defect in surface expression was not due to the absence of the glycan moiety, since the substitution of a glycine for a serine at amino acid 88 did not have the same drastic effect in the presence of human beta 2-microglobulin. These and other data suggest that the asparagine residue may play a critical role in the conformation of the HLA heavy chain and its interaction with beta 2-microglobulin. Immunofluorescence microscopy following permeabilization of the transfectants demonstrated that the unglycosylated HLA heavy chains are sequestered in an unidentified cellular compartment that is different from the Golgi structure.
Mol Cell Biol 1987 Mar
PMID:Amino acid sequences in the alpha 1 domain and not glycosylation are important in HLA-A2/beta 2-microglobulin association and cell surface expression. 355 Apr 37

Human promyelocytic leukemia (HL-60) cells were induced by 1,25-dihydroxyvitamin D3 (calcitriol) to differentiate and examined using a panel of monoclonal antibodies (MoAbs) and functional assays. Although morphologically and histochemically these cells appeared to be of the monocyte-macrophage phenotype, there was a decline in Fc receptors for IgGl and no induction of class II HLA antigens. There was, however, dramatic induction of the antigen detected by the myeloid-specific MoAb AML-2-23. These data suggest that the phenotypic changes induced by calcitriol in HL-60 cells are consistent with myelomonocytic differentiation in that the resultant cells possess characteristics of both monocytes (morphology, non-specific esterase staining, high levels of AML-2-23 reactivity) and granulocytes (PMN 29 binding, decreased Fc receptors for IgGl, absence of class II HLA antigens). Perhaps more important, the ability of calcitriol-treated cells to perform antibody-dependent cellular cytotoxicity and phagocytosis was markedly augmented. Lysis of antibody-coated erythrocytes by HL-60 cells increased from 5% in controls to 30-35% with calcitriol treatment for 4 days. This enhanced effector cell function was seen despite a decline in Fc receptors measured by cytofluorography. These data suggest that calcitriol may be involved in both differential and functional activation of myeloid cells.
Mol Immunol 1985 May
PMID:1,25-Dihydroxyvitamin D3 induces a myelomonocytic phenotype with enhanced effector cell function in the HL-60 promyelocytic leukemia cell line. 386 Jul 30

Recent studies [Marsh et al. (1982) J. exp. Med. 155, 1439-1451; Coulter (1983) M.Sc. thesis, McGill University, Montreal, Canada; Coulter et al. (1983) in Genetic and Environmental Factors in Clinical Allergy (Edited by Marsh D.G., Blumenthal M.N. and Santilli J., Jr), University of Minnesota Press, Minneapolis, MN] have shown a highly significant association between HLA-Dw2/DR2 and host sensitivity to the 5000-D, 4-disulfide bonded protein Ra5S of short ragweed pollen. To extend these findings, we isolated Ra5G, an Ra5S-like protein, from giant ragweed pollen by gel and ion-exchange chromatography. The protein was homogeneous by polyacrylamide gel electrophoresis (pH 4.3), reverse-phase high-performance liquid chromatography, and antigenic assays. Its mol. wt and amino acid composition (including 8 half-cystine residues) were closely similar to Ra5S, but the two proteins had little or no antigenic or allergenic cross-reactivity. In a study of 200 ragweed-sensitive individuals, host sensitivity simultaneously to Ra5G and Ra5S was significantly associated with the DR2 allele. The amino acid sequence of Ra5G was determined and showed close homology with Ra5S. The potential function of a highly homologous decapeptidyl sequence stretch is discussed in relation to Ir gene control of immune response to the 2 proteins.
Mol Immunol 1985 Aug
PMID:Ra5G, a homologue of Ra5 in giant ragweed pollen: isolation, HLA-DR-associated activity and amino acid sequence. 386 54

A monoclonal antibody designated as C21 reacting with a p43,12 complex was developed against human thymocytes. It stained predominantly the early hematopoietic cells of the lymphoid lineage and also thymocytes, peripheral B-cells and activated T- and B-cells similarly to OKT10. The heavy chain of this antigen was a glycoprotein of Mr 43,000 (p43). Sequential immunoprecipitation with C21 and OKT10 antibodies indicated that they both reacted with an identical heavy-chain molecule. This observation was further documented by two-dimensional analysis. Monoclonal antibody C21 was used to probe a p43,12 complex further. Structural polymorphism of the p43 heavy chain isolated from T- and B-cells of different individuals was not detected by chymotryptic peptide mapping, although molecules from these cell types possessed a different charge on two-dimensional gels. An unusual observation was made regarding this complex on MOLT4 cells. The light chain co-precipitated from these cells was 12,000 daltons and had a pI distinct from that of beta 2-microglobulin but similar to the pI of the beta t molecule. Comparison between chymotryptic peptide maps of the p43 heavy chain and those of the human and murine class I molecules such as HLA, T6, H-2K, Qa-2 and TL revealed no apparent homology. We have shown, however, that the peptide backbone of p43, as studied by both tunicamycin treatment of cells and endoglycosidase F digestion of immunoprecipitates, was identical in size to that of murine Qa-1. These results suggest that the p43 antigen may be homologous to murine Qa-1 or another class I antigen encoded in the murine TL:Qa region.
Mol Immunol 1985 Jun
PMID:Biochemical characterization of a p43,12 complex: comparison with human and murine class I molecules. 387 19

Secretion of Igs and surface expression of HLA antigens was examined in lymphoid cells as a function of temp. Upon reducing the temp from 37 to 20 degrees C a progressive decrease in the secretion of Ig and surface expression of HLA antigens was noted. When the status of the oligosaccharides present on these glycoproteins was examined, conversion of high-mannose [endo-beta-N-acetylglucosaminidase-(Endo H) sensitive] to complex-type (Endo H resistant) oligosaccharides diminished with decreasing temp. At no time was an accumulation of Endo H resistant glycoproteins seen intracellularly. These results show that the phenomenon observed for synthesis and intracellular transport of viral glycoproteins in epithelial cells at reduced temp, namely intracellular accumulation of viral glycoproteins carrying complex sugar moieties, does not necessarily apply to glycoprotein transport in lymphoid cells. A difference in subcellular organization of epithelial and lymphoid cells may be responsible for this discrepancy.
Mol Immunol 1985 Jul
PMID:Effect of reduced temperature on glycoprotein (Ig, HLA) processing and transport in lymphoid cells. 387 89

A variant of the human neuroblastoma cell line, IMR-5, was selected by a series of treatments with the monoclonal antibody PI153/3 and complement. The variant, M-1, was not reactive by either cytotoxicity or binding assays with the PI153/3 antibody or with two other monoclonal antibodies that were selected on the basis of their inhibition of PI153/3 binding. Although no antigen could be detected on the cell surface or in the supernatant of the variant cell line, a reduced level of binding could be detected in M1 cell extracts compared to extracts of IMR5. The variant cell line did not differ from IMR5 in its sensitivity in lysis by other antibodies, in its lack of expression of HLA antigens, or in its capacity to form tumors in nude mice.
Somat Cell Mol Genet 1985 Sep
PMID:Selection of variant neuroblastoma cell line which has lost cell surface expression of antigen detected by monoclonal antibody PI153/3. 389 5

Bovine beta 2-microglobulin (beta 2-m) present in fetal calf serum (FCS) is able to replace endogenous beta 2-m associated with several class I antigens from human and mouse cells maintained in culture [Bernabeu et al. (1984) Nature, Lond. 308, 642-645]. Here we show that human HLA-A2 and HLA-B7, as well as mouse H-2Ld and H-2Dd heavy chains expressed after gene transfer in mouse L-cells, associate to a large extent with bovine beta 2-m. We also demonstrate that bovine beta 2-m associated with the endogenous H-2Kk/Dk heavy chains generates an antibody response when L-cells are injected into syngeneic C3H mice.
Mol Immunol 1985 Aug
PMID:beta 2-Microglobulin from serum associates with several class I antigens expressed on the surface of mouse L-cells. 390 Jun 96


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