Home LiteratureArticle Details
PMID: 1696010 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Definition of a physiologic aging autoantigen by using synthetic peptides of membrane protein band 3: localization of the active antigenic sites.

Kay MM, Marchalonis JJ, Hughes J, Watanabe K, Schluter SF

Abstract

Senescent cell antigen (SCA), an aging antigen, is a protein that appears on old cells and marks them for removal by the immune system in mammals. It is derived from band 3, a ubiquitous membrane transport protein found in diverse cell types and tissues. We have used synthetic peptides to identify aging antigenic sites on band 3, using a competitive inhibition assay and immunoblotting with IgG directed against the aging antigen on old cells. Results indicate that: (i) the active antigenic sites of the aging antigen reside on membrane protein band 3 residues that are extracellular regions implicated in anion transport (residues 538-554 and 788-827); (ii) a putative ankyrin-binding-region peptide is not involved in SCA activity; and (iii) carbohydrate moieties are not required for the antigenicity or recognition of SCA because synthetic peptides alone abolish binding of senescent cell IgG to erythrocytes. One of the putative transport sites that contributes to the aging antigen is located toward the carboxyl terminus. A model of band 3 is presented. Localization of the active antigenic site on the band 3 molecule facilitates definition of the molecular changes occurring during aging that initiate molecular as well as cellular degeneration.

MeSH Terms
Amino Acid Sequence Anion Exchange Protein 1, Erythrocyte/immunology Antigen-Antibody Complex Antigens, Differentiation/analysis Binding, Competitive Electrophoresis, Polyacrylamide Gel Epitopes/analysis Erythrocyte Aging/immunology Erythrocyte Membrane/ultrastructure Humans Immunoglobulin G/isolation & purification Models, Molecular Molecular Sequence Data Peptides/chemical synthesis Protein Conformation
Chemicals
Anion Exchange Protein 1, Erythrocyte Antigen-Antibody Complex Antigens, Differentiation Epitopes Immunoglobulin G Peptides senescent cell differentiation antigen
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kay M M
Department of Medicine, Texas A&M University, Temple 76503.
Marchalonis J J
Hughes J
Watanabe K
Schluter S F
References (37)
37 references, click to expand
  1. Mechanism of removal of senescent cells by human macrophages in situ.
    Proc Natl Acad Sci U S A. 1975 Sep;72(9):3521-5 PMID: 1059140
  2. The organization of proteins in the human red blood cell membrane. A review.
    J Cell Biol. 1974 Jul;62(1):1-19 PMID: 4600883
  3. The minimal structure containing the band 3 anion transport site. A 35Cl NMR study.
    J Biol Chem. 1985 Oct 25;260(24):13294-303 PMID: 4055737
  4. Erythrocyte aging: a comparison of model systems for simulating cellular aging in vitro.
    Blood Cells. 1988;14(1):19-46 PMID: 3179456
  5. Oxidation as a possible mechanism of cellular aging: vitamin E deficiency causes premature aging and IgG binding to erythrocytes.
    Proc Natl Acad Sci U S A. 1986 Apr;83(8):2463-7 PMID: 3458208
  6. Two types of collecting duct mitochondria-rich (intercalated) cells: lectin and band 3 cytochemistry.
    Am J Physiol. 1986 Sep;251(3 Pt 1):C347-55 PMID: 3529979
  7. Functional topography of band 3: specific structural alteration linked to functional aberrations in human erythrocytes.
    Proc Natl Acad Sci U S A. 1988 Jan;85(2):492-6 PMID: 2829189
  8. Erythrocyte homeostasis: antibody-mediated recognition of the senescent state by macrophages.
    Proc Natl Acad Sci U S A. 1986 Aug;83(15):5498-501 PMID: 3016705
  9. A 115-kD polypeptide immunologically related to erythrocyte band 3 is present in Golgi membranes.
    Science. 1988 Dec 2;242(4883):1308-11 PMID: 2461589
  10. Alteration in membrane protein band 3 associated with accelerated erythrocyte aging.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5834-8 PMID: 2527366
  11. Primary structure of the rat kidney band 3 anion exchange protein deduced from a cDNA.
    J Biol Chem. 1989 May 15;264(14):8185-92 PMID: 2722777
  12. The complete amino acid sequence of the human erythrocyte membrane anion-transport protein deduced from the cDNA sequence.
    Biochem J. 1988 Dec 15;256(3):703-12 PMID: 3223947
  13. Life and death of neurons: the role of senescent cell antigen.
    Ann N Y Acad Sci. 1988;521:155-69 PMID: 3377362
  14. Localization of senescent cell antigen on band 3.
    Proc Natl Acad Sci U S A. 1984 Sep;81(18):5753-7 PMID: 6207531
  15. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.
    Annu Rev Biophys Biophys Chem. 1986;15:321-53 PMID: 3521657
  16. Immunolocalization of band 3 protein in normal and cystic fibrosis skin.
    J Histochem Cytochem. 1986 Jun;34(6):823-6 PMID: 3517151
  17. Evidence for a malarial parasite interaction site on the major transmembrane protein of the human erythrocyte.
    Science. 1985 Apr 5;228(4695):75-7 PMID: 3883494
  18. Membrane channel protein abnormalities and autoantibodies in neurological disease.
    Brain Res Bull. 1990 Jan;24(1):105-11 PMID: 1690071
  19. Selective phenylglyoxalation of functionally essential arginyl residues in the erythrocyte anion transport protein.
    J Gen Physiol. 1983 Apr;81(4):453-84 PMID: 6854266
  20. Immune elimination of autologous senescent erythrocytes by Kupffer cells in vivo.
    Cell Immunol. 1983 Sep;80(2):426-30 PMID: 6688379
  21. Polypeptides immunologically related to band 3 are present in nucleated somatic cells.
    Proc Natl Acad Sci U S A. 1983 Nov;80(22):6882-6 PMID: 6196779
  22. Antigenicity, storage, and aging: physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen.
    Mol Cell Biochem. 1982 Nov 26;49(2):65-85 PMID: 6185837
  23. A comprehensive set of sequence analysis programs for the VAX.
    Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387-95 PMID: 6546423
  24. Senescent cell antigen is immunologically related to band 3.
    Proc Natl Acad Sci U S A. 1983 Mar;80(6):1631-5 PMID: 6572929
  25. Phagocytosis of sickle erythrocytes: immunologic and oxidative determinants of hemolytic anemia.
    Blood. 1984 Sep;64(3):733-41 PMID: 6466875
  26. The effect of donor and cell age on several characteristics of rat erythrocytes.
    Exp Hematol. 1983 Nov;11(10):987-95 PMID: 6662217
  27. Anion transport in red blood cells and arginine specific reagents. (1). Effect of chloride and sulfate ions on phenylglyoxal sensitive sites in the red blood cell membrane.
    Biochem Biophys Res Commun. 1983 Jan 27;110(2):616-24 PMID: 6838541
  28. Binding of autologous IgG to human red blood cells before and after ATP-depletion. Selective exposure of binding sites (autoantigens) on spectrin-free vesicles.
    Biochim Biophys Acta. 1983 Apr 6;729(2):249-57 PMID: 6830791
  29. Aging of the erythrocyte. XVII. Binding of autologous immunoglobulin G.
    Mech Ageing Dev. 1982 Nov;20(3):223-32 PMID: 7162219
  30. Detection of IgG sensitization of red cells with 125I staphylococcal protein A.
    Am J Hematol. 1982 Jun;12(4):337-46 PMID: 7114050
  31. A simple method for displaying the hydropathic character of a protein.
    J Mol Biol. 1982 May 5;157(1):105-32 PMID: 7108955
  32. Homeostatic removal of senescent murine erythrocytes by splenic macrophages.
    Exp Hematol. 1981 Mar;9(3):297-307 PMID: 7227479
  33. Isolation of the phagocytosis-inducing IgG-binding antigen on senescent somatic cells.
    Nature. 1981 Feb 5;289(5797):491-4 PMID: 7464917
  34. Anion transport across the erythrocyte membrane, in situ proteolysis of band 3 protein, and cross-linking of proteolytic fragments by 4,4'-diisothiocyano dihydrostilbene-2,2'-disulfonate.
    Biochim Biophys Acta. 1979 Jul 5;554(2):498-519 PMID: 486455
  35. Role of physiologic autoantibody in the removal of senescent human red cells.
    J Supramol Struct. 1978;9(4):555-67 PMID: 108480
  36. Immunoreactive forms of human erythrocyte ankyrin are present in diverse cells and tissues.
    Nature. 1979 Oct 18;281(5732):597-9 PMID: 492324
  37. Monoclonal antibodies against human erythrocyte band 3 protein. Localization of proteolytic cleavage sites and stilbenedisulfonate-binding lysine residues.
    J Biol Chem. 1986 Jul 5;261(19):9002-10 PMID: 3087983
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
1990-08-00
Pages
5734-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC54402
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com