Polyspecificity of Antistreptococcal Murine Monoclonal Antibodies and Their Implications in Autoimmunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1986 Oct 1

PMID 3531385

Citations 26

Authors

M W Cunningham

R A Swerlick

Affiliations

Soon will be listed here.

Abstract

mAbs produced by immunization of BALB/c mice with Streptococcus pyogenes M type 5 membranes were further characterized for their reaction with S. pyogenes pep M5 protein and with autoantigens associated with human cell lines. mAbs 36.2.2 and 54.2.8 simultaneously reacted with M protein and a membrane protein(s) of S. pyogenes. When cell lines were mixed with 54.2.8, we saw nuclear fluorescence along with staining of the cytoskeleton. Subsequent experiments revealed that 54.2.8 was an anti-DNA antibody that reacted with DNA, poly(I), poly(dT), and weakly with cardiolipin. Its reactivity with the cytoskeleton could be blocked with anti-vimentin. On the other hand, 36.2.2 reacted with the cytoskeleton, sparing the nucleus, and was inhibited by the alpha helical proteins myosin, actin, and keratin. mAb 54.2.8 was inhibited with myosin, but not with actin and keratin. None of the antibodies studied were inhibited by collagen, and none of them were rheumatoid factors. The results imply that Group A streptococci can activate B cell clones against myosin, alpha helical proteins, or DNA, thereby contributing to the enhancement of autoantibody production.

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References

Krisher K, Cunningham M . Myosin: a link between streptococci and heart. Science. 1985; 227(4685):413-5. DOI: 10.1126/science.2578225. View

Shoenfeld Y, Schwartz R . Immunologic and genetic factors in autoimmune diseases. N Engl J Med. 1984; 311(16):1019-29. DOI: 10.1056/NEJM198410183111605. View

Manjula B, Trus B, Fischetti V . Presence of two distinct regions in the coiled-coil structure of the streptococcal Pep M5 protein: relationship to mammalian coiled-coil proteins and implications to its biological properties. Proc Natl Acad Sci U S A. 1985; 82(4):1064-8. PMC: 397194. DOI: 10.1073/pnas.82.4.1064. View

Poirier T, Kehoe M, Dale J, Timmis K, Beachey E . Expression of protective and cardiac tissue cross-reactive epitopes of type 5 streptococcal M protein in Escherichia coli. Infect Immun. 1985; 48(1):198-203. PMC: 261935. DOI: 10.1128/iai.48.1.198-203.1985. View

Carroll P, Stafford D, Schwartz R, Stollar B . Murine monoclonal anti-DNA autoantibodies bind to endogenous bacteria. J Immunol. 1985; 135(2):1086-90. View

Dale J, Beachey E . Epitopes of streptococcal M proteins shared with cardiac myosin. J Exp Med. 1985; 162(2):583-91. PMC: 2187745. DOI: 10.1084/jem.162.2.583. View

Cunningham M, Hall N, Krisher K, Spanier A . A study of anti-group A streptococcal monoclonal antibodies cross-reactive with myosin. J Immunol. 1986; 136(1):293-8. View

Kaplan M . IMMUNOLOGIC RELATION OF STREPTOCOCCAL AND TISSUE ANTIGENS. I. PROPERTIES OF AN ANTIGEN IN CERTAIN STRAINS OF GROUP A STREPTOCOCCI EXHIBITING AN IMMUNOLOGIC CROSS-REACTION WITH HUMAN HEART TISSUE. J Immunol. 1963; 90:595-606. View

Kaplan M, BOLANDE R, RAKITA L, Blair J . PRESENCE OF BOUND IMMUNOGLOBULINS AND COMPLEMENT IN THE MYOCARDIUM IN ACUTE RHEUMATIC FEVER. ASSOCIATION WITH CARDIAC FAILURE. N Engl J Med. 1964; 271:637-45. DOI: 10.1056/NEJM196409242711301. View

10.

NACHLAS M, Monis B, ROSENBATT D, Seligman A . Improvement in the histochemical localization of leucine aminopeptidase with a new substrate, L-leucyl-4-methoxy-2-naphthylamide. J Biophys Biochem Cytol. 1960; 7:261-4. PMC: 2224813. DOI: 10.1083/jcb.7.2.261. View

11.

Zabriskie J, FREIMER E . An immunological relationship between the group. A streptococcus and mammalian muscle. J Exp Med. 1966; 124(4):661-78. PMC: 2138256. DOI: 10.1084/jem.124.4.661. View

12.

LYAMPERT I, Borodiyuk N, Ugryumova G . The reaction of heart and other organ extracts with the sera of animals immunized with group A streptococci. Immunology. 1968; 15(6):845-54. PMC: 1409493. View

13.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

14.

Zabriskie J, Hsu K, SEEGAL B . Heart-reactive antibody associated with rheumatic fever: characterization and diagnostic significance. Clin Exp Immunol. 1970; 7(2):147-59. PMC: 1712832. View

15.

Das S, Cassidy J, Petty R . Antibodies against heart muscle and nuclear constituents in cardiomyopathy. Am Heart J. 1972; 83(2):159-66. DOI: 10.1016/0002-8703(72)90134-2. View

16.

Gambrell Jr S, Allen Jr J . Stress concentrations at the apex of pinned, implanted teeth. J Dent Res. 1976; 55(1):59-65. DOI: 10.1177/00220345760550012501. View

17.

Lieber M, Smith B, Szakal A, Todaro G . A continuous tumor-cell line from a human lung carcinoma with properties of type II alveolar epithelial cells. Int J Cancer. 1976; 17(1):62-70. DOI: 10.1002/ijc.2910170110. View

18.

Husby G, van de Rijn I, Zabriskie J, Abdin Z, Williams Jr R . Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever. J Exp Med. 1976; 144(4):1094-110. PMC: 2190435. DOI: 10.1084/jem.144.4.1094. View

19.

van de Rijn I, Zabriskie J, McCarty M . Group A streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen. J Exp Med. 1977; 146(2):579-99. PMC: 2180771. DOI: 10.1084/jem.146.2.579. View

20.

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View