A possible new bridge between innate and adaptive immunity: Are the anti-mitochondrial citrate synthase autoantibodies components of the natural antibody network?

T. Czömpöly, Katalin Olasz, Diána Simon, Zoltán Nyárády, L. Pálinkás, L. Czirják, T. Berki, P. Németh

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16 Citations (Scopus)

Abstract

Natural antibody (nAb) producing B-1 B cells are considered an intermediate stage of evolution between innate and adaptive immunity. nAbs are immunoglobulins that are produced without antigen priming. nAbs can recognize foreign targets and may serve in the first line of immune defense during an infection. Natural autoantibodies (nAAbs) present in the serum of both healthy humans and patients suffering from systemic autoimmune diseases recognize a set of evolutionarily conserved self-structures. Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign (non-self) to essential (self) molecules. We investigated the possible overlap in recognized epitopes of innate and self-reactive nAbs and surveyed changes in physiological autoreactivity under pathological autoimmune conditions. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) (EC 2.3.3.1) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAAbs with IgM isotype. We analyzed cross reactive epitopes on human CS, bacterial CS, and various standard autoantigens. The anti-CS nAAbs by participating in the nAb network, could function in innate defense mechanisms and at the same time recognize a target antigen (nucleosome) in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible new link between the innate like component and the adaptive-autoimmune arm of the humoral immune system.

Original languageEnglish
Pages (from-to)1761-1768
Number of pages8
JournalMolecular Immunology
Volume43
Issue number11
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Citrate (si)-Synthase
Adaptive Immunity
Innate Immunity
Autoantibodies
Antibodies
Autoimmune Diseases
Epitopes
Epitope Mapping
Antigens
Peptide Library
Nucleosomes
Autoantigens
Mitochondrial Membranes
Serum
Immunoglobulin M
Immunoglobulins
Immune System
Mitochondria
B-Lymphocytes
Enzymes

Keywords

  • Autoimmunity
  • Epitope mapping
  • Mitochondrial inner membrane enzyme
  • Multi-pin ELISA
  • Natural antibody
  • Phage display
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

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title = "A possible new bridge between innate and adaptive immunity: Are the anti-mitochondrial citrate synthase autoantibodies components of the natural antibody network?",
abstract = "Natural antibody (nAb) producing B-1 B cells are considered an intermediate stage of evolution between innate and adaptive immunity. nAbs are immunoglobulins that are produced without antigen priming. nAbs can recognize foreign targets and may serve in the first line of immune defense during an infection. Natural autoantibodies (nAAbs) present in the serum of both healthy humans and patients suffering from systemic autoimmune diseases recognize a set of evolutionarily conserved self-structures. Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign (non-self) to essential (self) molecules. We investigated the possible overlap in recognized epitopes of innate and self-reactive nAbs and surveyed changes in physiological autoreactivity under pathological autoimmune conditions. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) (EC 2.3.3.1) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAAbs with IgM isotype. We analyzed cross reactive epitopes on human CS, bacterial CS, and various standard autoantigens. The anti-CS nAAbs by participating in the nAb network, could function in innate defense mechanisms and at the same time recognize a target antigen (nucleosome) in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible new link between the innate like component and the adaptive-autoimmune arm of the humoral immune system.",
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AU - Czömpöly, T.

AU - Olasz, Katalin

AU - Simon, Diána

AU - Nyárády, Zoltán

AU - Pálinkás, L.

AU - Czirják, L.

AU - Berki, T.

AU - Németh, P.

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AB - Natural antibody (nAb) producing B-1 B cells are considered an intermediate stage of evolution between innate and adaptive immunity. nAbs are immunoglobulins that are produced without antigen priming. nAbs can recognize foreign targets and may serve in the first line of immune defense during an infection. Natural autoantibodies (nAAbs) present in the serum of both healthy humans and patients suffering from systemic autoimmune diseases recognize a set of evolutionarily conserved self-structures. Because of their endosymbiotic evolutionary origin, proteins compartmentalized into mitochondria represent an interesting transition from prokaryotic foreign (non-self) to essential (self) molecules. We investigated the possible overlap in recognized epitopes of innate and self-reactive nAbs and surveyed changes in physiological autoreactivity under pathological autoimmune conditions. Epitope mapping analysis of a mitochondrial inner membrane enzyme, citrate synthase (CS) (EC 2.3.3.1) by synthetic overlapping peptides and phage display libraries using sera from healthy individuals and from patients having systemic autoimmune disease revealed CS recognizing nAAbs with IgM isotype. We analyzed cross reactive epitopes on human CS, bacterial CS, and various standard autoantigens. The anti-CS nAAbs by participating in the nAb network, could function in innate defense mechanisms and at the same time recognize a target antigen (nucleosome) in a systemic autoimmune disease. Thus, at the level of recognized epitopes there is a possible new link between the innate like component and the adaptive-autoimmune arm of the humoral immune system.

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