Polyclonal antibodies to the encephalitogenic neighborhoods of myelin basic protein: Singular affinity populations neutralized by specific synthetic peptide probes

Eugene D. Day, George A. Hashim, Donna J. Ireland, Nicholas Potter

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Specific ligand neutralization was used to probe the extent to which singular antibody affinity populations signified specific determinants in the neighborhood of myelin basic protein (MBP) encephalitogens. The probes were individual members of a panel of synthetic peptide analogs subsuming encephalitogenic regions. Comparative Scatchard analyses of neutralized and unneutralized antisera helped to identify the particular peptide determinants involved in the original polyclonal antibody responses to the multiple antigenic determinants of encephalitogenic peptides. The range of affinities for an antibody population against a singular MBP peptide determinant was found to be relatively restricted while the range of affinities overall for all populations within a given antipeptide antiserum was found to be relatively wide and invariably discontinuous. Consequently, the individual discontinuous affinity populations could readily be dissected by application of the Rosenthal method of Scatchard curve analysis. It was found that the singular high affinity antibody population (5.6 × 1017 M-1) of a Lewis rat antiserum to rat encephalitogenic GSLPQKAQRPQDENG (S49) was against a determinant near the N-terminal non-encephalitogenic end of the peptide. Only the low affinity antibody populations were found that had reactivity for determinants within the encephalitogenic region itself. The singular high affinity antibody population (5.97 × 107 M-) of a rabbit antiserum to rabbit encephalitogenic TTHYGSLPQKAQGHRPQDEG (S82) was against a determinant centered about the tyrosyl residue, within the encephalitogenic region for the rabbit, but was completely cross-reactive with a specific circulating endogenous inhibitor. The results obtained with the rat and rabbit EAE sera were consistent with a previously advanced hypothesis that antibodies to determinants within encephalitogenic neighborhoods would effectively block the onset of EAE if high enough in affinity and not neutralized by an endogenous inhibitor.

Original languageEnglish (US)
Pages (from-to)143-158
Number of pages16
JournalJournal of Neuroimmunology
Volume13
Issue number2
DOIs
StatePublished - Jan 1 1986
Externally publishedYes

Fingerprint

Myelin Basic Protein
Antibody Affinity
Peptides
Antibodies
Immune Sera
Population
Rabbits
Antibody Formation
Epitopes
Ligands
Serum

All Science Journal Classification (ASJC) codes

  • Immunology
  • Immunology and Allergy
  • Clinical Neurology
  • Neurology

Cite this

Polyclonal antibodies to the encephalitogenic neighborhoods of myelin basic protein : Singular affinity populations neutralized by specific synthetic peptide probes. / Day, Eugene D.; Hashim, George A.; Ireland, Donna J.; Potter, Nicholas.

In: Journal of Neuroimmunology, Vol. 13, No. 2, 01.01.1986, p. 143-158.

Research output: Contribution to journalArticle

@article{a580e810971a43d895ef4f508ca09141,
title = "Polyclonal antibodies to the encephalitogenic neighborhoods of myelin basic protein: Singular affinity populations neutralized by specific synthetic peptide probes",
abstract = "Specific ligand neutralization was used to probe the extent to which singular antibody affinity populations signified specific determinants in the neighborhood of myelin basic protein (MBP) encephalitogens. The probes were individual members of a panel of synthetic peptide analogs subsuming encephalitogenic regions. Comparative Scatchard analyses of neutralized and unneutralized antisera helped to identify the particular peptide determinants involved in the original polyclonal antibody responses to the multiple antigenic determinants of encephalitogenic peptides. The range of affinities for an antibody population against a singular MBP peptide determinant was found to be relatively restricted while the range of affinities overall for all populations within a given antipeptide antiserum was found to be relatively wide and invariably discontinuous. Consequently, the individual discontinuous affinity populations could readily be dissected by application of the Rosenthal method of Scatchard curve analysis. It was found that the singular high affinity antibody population (5.6 × 1017 M-1) of a Lewis rat antiserum to rat encephalitogenic GSLPQKAQRPQDENG (S49) was against a determinant near the N-terminal non-encephalitogenic end of the peptide. Only the low affinity antibody populations were found that had reactivity for determinants within the encephalitogenic region itself. The singular high affinity antibody population (5.97 × 107 M-) of a rabbit antiserum to rabbit encephalitogenic TTHYGSLPQKAQGHRPQDEG (S82) was against a determinant centered about the tyrosyl residue, within the encephalitogenic region for the rabbit, but was completely cross-reactive with a specific circulating endogenous inhibitor. The results obtained with the rat and rabbit EAE sera were consistent with a previously advanced hypothesis that antibodies to determinants within encephalitogenic neighborhoods would effectively block the onset of EAE if high enough in affinity and not neutralized by an endogenous inhibitor.",
author = "Day, {Eugene D.} and Hashim, {George A.} and Ireland, {Donna J.} and Nicholas Potter",
year = "1986",
month = "1",
day = "1",
doi = "10.1016/0165-5728(86)90061-5",
language = "English (US)",
volume = "13",
pages = "143--158",
journal = "Journal of Neuroimmunology",
issn = "0165-5728",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Polyclonal antibodies to the encephalitogenic neighborhoods of myelin basic protein

T2 - Singular affinity populations neutralized by specific synthetic peptide probes

AU - Day, Eugene D.

AU - Hashim, George A.

AU - Ireland, Donna J.

AU - Potter, Nicholas

PY - 1986/1/1

Y1 - 1986/1/1

N2 - Specific ligand neutralization was used to probe the extent to which singular antibody affinity populations signified specific determinants in the neighborhood of myelin basic protein (MBP) encephalitogens. The probes were individual members of a panel of synthetic peptide analogs subsuming encephalitogenic regions. Comparative Scatchard analyses of neutralized and unneutralized antisera helped to identify the particular peptide determinants involved in the original polyclonal antibody responses to the multiple antigenic determinants of encephalitogenic peptides. The range of affinities for an antibody population against a singular MBP peptide determinant was found to be relatively restricted while the range of affinities overall for all populations within a given antipeptide antiserum was found to be relatively wide and invariably discontinuous. Consequently, the individual discontinuous affinity populations could readily be dissected by application of the Rosenthal method of Scatchard curve analysis. It was found that the singular high affinity antibody population (5.6 × 1017 M-1) of a Lewis rat antiserum to rat encephalitogenic GSLPQKAQRPQDENG (S49) was against a determinant near the N-terminal non-encephalitogenic end of the peptide. Only the low affinity antibody populations were found that had reactivity for determinants within the encephalitogenic region itself. The singular high affinity antibody population (5.97 × 107 M-) of a rabbit antiserum to rabbit encephalitogenic TTHYGSLPQKAQGHRPQDEG (S82) was against a determinant centered about the tyrosyl residue, within the encephalitogenic region for the rabbit, but was completely cross-reactive with a specific circulating endogenous inhibitor. The results obtained with the rat and rabbit EAE sera were consistent with a previously advanced hypothesis that antibodies to determinants within encephalitogenic neighborhoods would effectively block the onset of EAE if high enough in affinity and not neutralized by an endogenous inhibitor.

AB - Specific ligand neutralization was used to probe the extent to which singular antibody affinity populations signified specific determinants in the neighborhood of myelin basic protein (MBP) encephalitogens. The probes were individual members of a panel of synthetic peptide analogs subsuming encephalitogenic regions. Comparative Scatchard analyses of neutralized and unneutralized antisera helped to identify the particular peptide determinants involved in the original polyclonal antibody responses to the multiple antigenic determinants of encephalitogenic peptides. The range of affinities for an antibody population against a singular MBP peptide determinant was found to be relatively restricted while the range of affinities overall for all populations within a given antipeptide antiserum was found to be relatively wide and invariably discontinuous. Consequently, the individual discontinuous affinity populations could readily be dissected by application of the Rosenthal method of Scatchard curve analysis. It was found that the singular high affinity antibody population (5.6 × 1017 M-1) of a Lewis rat antiserum to rat encephalitogenic GSLPQKAQRPQDENG (S49) was against a determinant near the N-terminal non-encephalitogenic end of the peptide. Only the low affinity antibody populations were found that had reactivity for determinants within the encephalitogenic region itself. The singular high affinity antibody population (5.97 × 107 M-) of a rabbit antiserum to rabbit encephalitogenic TTHYGSLPQKAQGHRPQDEG (S82) was against a determinant centered about the tyrosyl residue, within the encephalitogenic region for the rabbit, but was completely cross-reactive with a specific circulating endogenous inhibitor. The results obtained with the rat and rabbit EAE sera were consistent with a previously advanced hypothesis that antibodies to determinants within encephalitogenic neighborhoods would effectively block the onset of EAE if high enough in affinity and not neutralized by an endogenous inhibitor.

UR - http://www.scopus.com/inward/record.url?scp=0023005735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023005735&partnerID=8YFLogxK

U2 - 10.1016/0165-5728(86)90061-5

DO - 10.1016/0165-5728(86)90061-5

M3 - Article

C2 - 2430996

AN - SCOPUS:0023005735

VL - 13

SP - 143

EP - 158

JO - Journal of Neuroimmunology

JF - Journal of Neuroimmunology

SN - 0165-5728

IS - 2

ER -