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PMID: 5033419 Published · ppublish English Journal Article

Experimental allergic encephalitis. Dissociation of cellular immunity to brain protein and disease production.

The Journal of experimental medicine ·Vol. 136 ·No. 1 ·1972-07-01 ·Pages 156-74

Spitler LE, Von Muller CM, Fudenberg HH, Eylar EH

Abstract

The encephalitogenic determinant of brain protein, a nonapeptide having the amino acid sequence Phe-Ser-Trp-Gly-Ala-Glu-Gly-Gln-Lys, has been characterized and synthesized. In a previous study, analogues of this encephalitogenic peptide were synthesized and some were shown to be encephalitogenic while others were not. Guinea pigs were immunized with encephalitogenic peptides having amino acid sequences different from that in the native protein. These guinea pigs did not show cellular immunity in vivo (skin reactivity) or in vitro (lymphocyte stimulation or macrophage migration inhibition) to the encephalitogenic brain protein (EP) although they did show cellular immunity to the immunizing antigenic peptide. Guinea pigs immunized with an encephalitogenic peptide having the same amino acid sequence as the brain protein, or with a nonencephalitogenic peptide having the same amino acid sequence as the native protein but lacking the terminal lysine, did develop cellular immunity to the EP. Animals immunized with EP showed cellular immunity to this protein, but not to the encephalitogenic peptides. Animals immunized with nonencephalitogenic protein (NEP), prepared by altering the tryptophan residue of EP, did not develop disease but did show cellular immunity in vitro and in vivo to the EP. Animals protected from disease by immunization with NEP similarly showed cellular immunity to EP. Thus, the results suggest a dissociation between cellular immunity to EP and the production of experimental allergic encephalitis (EAE). Animals immunized with the encephalitogenic peptides develop EAE, but do not show cellular immunity to EP, and animals immunized with NEP show cellular immunity to EP but do not develop EAE. A fresh approach to the examination of the pathogenesis of EAE is now possible through the use of these well-characterized antigens.

MeSH Terms
Amino Acid Sequence Animals Antigens Brain/immunology Brain Chemistry Cattle Cell Migration Inhibition Encephalomyelitis, Autoimmune, Experimental/etiology Guinea Pigs Hypersensitivity, Delayed Hypersensitivity, Immediate Immunity, Cellular Immunization Myelin Sheath/immunology Nerve Tissue Proteins Peptides/analysis Spinal Cord/immunology
Chemicals
Antigens Nerve Tissue Proteins Peptides
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Spitler L E
Von Muller C M
Fudenberg H H
Eylar E H
References (39)
39 references, click to expand
  1. Passive transfer of adjuvant-induced arthritis and allergic encephalomyelitis in rats using thoracic duct lymphocytes.
    Nature. 1969 Dec 27;224(5226):1322 PMID: 5359301
  2. Studies on acute disseminated encephalomyelitis produced experimentally in rhesus monkeys.
    J Exp Med. 1948 Oct 1;88(4):417-26 PMID: 18884901
  3. Amino acid sequence of the basic protein of the myelin membrane.
    Proc Natl Acad Sci U S A. 1970 Nov;67(3):1425-31 PMID: 5274468
  4. Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. I. Characterization of the phenomenon.
    J Exp Med. 1968 Dec 1;128(6):1237-54 PMID: 4176937
  5. In vitro demonstration of cellular sensitivity in allergic encephalomyelitis.
    J Exp Med. 1965 Dec 1;122(6):1161-71 PMID: 5873682
  6. Anti-adrenal cellular hypersensitivity in Addison's disease. IV. In vivo and in vitro investigations on the mitochondrial fraction.
    Clin Exp Immunol. 1970 May;6(5):733-9 PMID: 5477928
  7. Tuberculin type sensitivity to spinal cord antigen in rabbits with isoallergic encephalomyelitis.
    J Immunol. 1951 Apr;66(4):421-44 PMID: 14824544
  8. Studies of lymphocyte culture: products of sensitive lymphocyte-antigen interaction.
    J Immunol. 1969 Nov;103(5):1072-7 PMID: 5350967
  9. Specific inhibition of the in vitro migration of leucocytes in ulcerative colitis and Crohn's disease.
    Scand J Gastroenterol. 1967;2(3):214-21 PMID: 6050716
  10. The specificity of allergic reactions. I. Delayed versus Arthus hypersensitivity.
    J Exp Med. 1960 Apr 1;111:465-83 PMID: 13745824
  11. Studies on the immune response to a characterized antigenic determinant of the tobacco mosaic virus protein.
    J Exp Med. 1970 Jan 1;131(1):133-48 PMID: 5409944
  12. Suppression of allergic encephalomyelitis in rats by means of antibrain serum.
    J Exp Med. 1963 May 1;117:755-74 PMID: 13941827
  13. A factor stimulating DNA synthesis derived from the medium of leukocyte cultures.
    Nature. 1965 Nov 20;208(5012):794-5 PMID: 5868897
  14. Studies on hypersensitivity. I. Delayed and Arthustype skin reactivity to protein conjugates in guinea pigs.
    Immunology. 1959 Jan;2(1):53-63 PMID: 13640680
  15. Lymphocyte stimulation: transfer of cellular hypersensitivity to antigen in vitro.
    Science. 1969 Sep 5;165(3897):1014-6 PMID: 5804724
  16. Transfedotr of Allergic Encephalomyelitis by Lymph Node Cells in Inbred Guinea Pigs.
    Science. 1961 Sep 1;134(3479):619-20 PMID: 17780912
  17. Allergic encephalomyelitis: cleavage of the C-tryptophyl bond in the encephalitogenic basic protein from bovne myelin.
    Arch Biochem Biophys. 1969 Apr;131(1):215-22 PMID: 4305605
  18. Wiskott-Aldrich syndrome, a genetically determined cellular immunologic deficiency: clinical and laboratory responses to therapy with transfer factor.
    Proc Natl Acad Sci U S A. 1970 Oct;67(2):821-8 PMID: 5289024
  19. Experimental allergic encephalomyelitis: synthesis of disease-inducing site of the basic protein.
    Science. 1970 Jun 5;168(3936):1220-3 PMID: 5442707
  20. A colorimetric procedure for the quantitative determination of tryptophan residues in proteins.
    J Biol Chem. 1967 Dec 25;242(23):5771-6 PMID: 6073658
  21. Leukotactic factor produced by sensitized lymphocytes.
    Science. 1969 Mar 7;163(3871):1079-81 PMID: 5764874
  22. GAMMA-GLOBULIN PRODUCTION BY HUMAN LYMPHOCYTES IN VITRO.
    Exp Cell Res. 1963 Dec;32:592-5 PMID: 14099828
  23. DELAYED HYPERSENSITIVITY IN VITRO. I. THE SPECIFICITY OF INHIBITION OF CELL MIGRATION BY ANTIGENS.
    J Immunol. 1964 Aug;93:264-73 PMID: 14205621
  24. SOLID-PHASE PEPTIDE SYNTHESIS. 3. AN IMPROVED SYNTHESIS OF BRADYKININ.
    Biochemistry. 1964 Sep;3:1385-90 PMID: 14229685
  25. Studies on hypersensitivity. IV. The relationship between contact and delayed sensitivity: a study of the specificity of cellular immune reactions.
    J Exp Med. 1961 Mar 1;113:571-85 PMID: 13704282
  26. In vitro evidence for cellular hypersensitivity to glomerular-basement-membrane antigens in human glomerulonephritis.
    N Engl J Med. 1970 Sep 3;283(10):497-501 PMID: 4915006
  27. Experimental allergic encephalomyelitis. An encephalitogenic basic protein from bovine myelin.
    Arch Biochem Biophys. 1969 Jun;132(1):34-48 PMID: 4978347
  28. Further study of skin reactions in rabbits with experimental allergic encephalomyelitis: reactions to tests with purified white matter fractions; use of a quantitative technique for evaluating sensitivity production of sensitization and disease by intradermal injection of antigen without adjuvants.
    J Infect Dis. 1956 Nov-Dec;99(3):258-69 PMID: 13376924
  29. Delayed hypersensitivity to intrinsic factor in patients with pernicious anaemia.
    Med Exp Int J Exp Med. 1969;19(4):231-9 PMID: 5396093
  30. Transfer of allergic encephalomyelitis in rats by means of lymph node cells.
    J Exp Med. 1960 Jan 1;111:119-36 PMID: 14430853
  31. Studies on hypersensitivity. III. The relation between delayed reactivity to the picryl group of conjugates and contact sensitivity.
    Immunology. 1959 Jul;2:219-29 PMID: 13798685
  32. In vitro delayed (cellular) hypersensitivity in multiple sclerosis to central nervous system antigens.
    Int Arch Allergy Appl Immunol. 1970;39(4):361-7 PMID: 5473642
  33. Reactions in vivo and in vitro produced by a soluble substance associated with delayed-type hypersensitivity.
    Proc Natl Acad Sci U S A. 1968 Mar;59(3):756-62 PMID: 5238658
  34. The Guillain-Barré syndrome and multiple sclerosis. In vitro cellular responses to nervous-tissue antigens.
    N Engl J Med. 1971 Apr 15;284(15):803-8 PMID: 4323673
  35. TRANSFER OF ALLERGIC ENCEPHALOMYELITIS IN RATS BY INTRACEREBRAL INJECTION OF LYMPHOID CELLS.
    Proc Soc Exp Biol Med. 1965 May;119:267-71 PMID: 14297867
  36. Delayed hypersensitivity in vitro: its mediation by cell-free substances formed by lymphoid cell-antigen interaction.
    Proc Natl Acad Sci U S A. 1966 Jul;56(1):72-7 PMID: 5229858
  37. Immune specific induction of interferon production in cultures of human blood lymphocytes.
    Science. 1969 Jun 20;164(3886):1415-7 PMID: 5783715
  38. Tuberculin-active carbohydrate that induces inhibition of macrophage migration but not lymphocyte transformation.
    Science. 1970 Nov 6;170(3958):637-9 PMID: 4919183
  39. Products of interaction of antigen-sensitized leukocytes and antigen: further characterization of the mitogenic factor.
    J Immunol. 1970 Mar;104(3):544-9 PMID: 5435785
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1972-07-01
Pages
156-74
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2139197
Subset
IM
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