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A serum factor cross-reactive with antibodies to a determinant of rabbit encephalitogenic sequence 65–74 of myelin basic protein

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Abstract

A serum factor. cross-reactive with antibodies to a defined determinant of myelin basic protein (residues 66–71), has been found in the sera of nine mammalian species where it may function as a specific neuroautotolerogen. In equilibrium competitive inhibition radioimmunoassays the factor appears to be completely competitive with synthetic peptide S24 (TTHYGSLPQKG) at high affinity and is therefore termed MBP-SF-24 (myelin basic protein serum factor of the S24 type). The bulk of the activity can be recovered by ammonium sulfate fractionation at 61.1% saturated ammonium sulfate (SAS), pH 7, (fractionE) after removal by precipitation at pH 7 of the 37.5, 42.6, 47.5, and 51.4% SAS fractions (fractionsA-D), including the immunoglobulins, and before removal by precipitation at pH 5 of the albumin fraction (fractionF). The factor, by its retention on XM300 during ultrafiltration of fractionE, can be purified 20-fold from serum proteins without much loss through a combination of SAS fractionation and ultrafiltration. The yield of MBP-SF-S24 in fractionE may range from a low 26 pmol S24 equivalents from 10 ml in sheep serum to a high 1.7 nmoles from 10 ml rat serum. The serum factor is reactive at high affinity with each of two populations of S24-reactive antibodies in one rabbit reagent antiserum and with one of two populations of S24-reactive antibodies in another. It appears to express a determinant involving residues THYGSL (66–71) of myelin basic protein with the same conformation as found in intact S24.

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Authors and Affiliations

  1. Department of Microbiology-Immunology, Duke University Medical Center, 27710, Durham, North Carolina

    Eugene D. Day (Javits Neuroscience Investigator) & Kenneth J. Lazarus

  2. Department of Surgery, Duke University Medical Center, 27710, Durham, North Carolina

    Eugene D. Day (Javits Neuroscience Investigator)

  3. Departments of Surgery and Microbiology, St. Luke's Hospital Center and Columbia University, 10025, New York, New York

    George A. Hashim

  4. Department of Microbiology-Immunology, The Medical and Dental Schools, 60611, Chicago, Illinois

    Philip Y. Paterson

  5. Department of Neurobiology/Physiology, Northwestern University, 60201, Evanston, Illinois

    Philip Y. Paterson

Authors
  1. Eugene D. Day
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  2. George A. Hashim
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  3. Kenneth J. Lazarus
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  4. Philip Y. Paterson
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Additional information

This work was supported at Duke University Medical Center by Research Grant NS-10237 from the National Institutes of Health of the U. S. Public Health Service and the Medical Scientist Training Program Grant #5-T32-OMO-7171-08; at St. Luke's Hospital Center by RG-1197-B-6 from the National Multiple Sclerosis Society and by a grant from the M.T. Biddle Foundation; and at Northwestern University by Research Grant NS-06262 from the National Institutes of Health of the U.S. Public Health Service.

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Day, E.D., Hashim, G.A., Lazarus, K.J. et al. A serum factor cross-reactive with antibodies to a determinant of rabbit encephalitogenic sequence 65–74 of myelin basic protein. Neurochem Res 10, 411–426 (1985). https://doi.org/10.1007/BF00964609

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