Binding of β2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells

Masataka Kuwana, Eiji Matsuura, Kazuko Kobayashi, Yuka Okazaki, Junichi Kaburaki, Yasuo Ikeda, Yutaka Kawakami

Research output: Contribution to journalArticle

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Abstract

Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasms proteins, such as β2-glycoprotein I (β2GPI). We have recently found that CD4+ T cells autoreactive to β 2GPI in patients with APS preferentially recognize a cryptic peptide encompassing amino acid residues 276-290 (p276-290), which contains the major PL-binding site, in the context of DR53. However, it is not clear how previously cryptic p276-290 becomes visible to the immune system and elicits a pathogenics autoimmune response to β2GPI. Here we show that presentation of a disease-relevant cryptic T-cell determinant in β2GPI is induced as a direct consequence of antigen processing from β2GPI bound to anionic PL. Dendritic cells or macrophages pulsed with PL-bound β2GPI induced a response of p276-290-specific CD4+ T-cell lines generated from the patients in an HLA-DR-restricted and antigen-processing-dependent manner but those with β2GPI or PL alone did not. In addition, the p276-290-reactive T-cell response was primed by stimulating peripheral blood T cells from DR53-carrying healthy individuals with dendritic cells bearing PL-bound β2GPI in vitro. Our finding is the first demonstration of an in vitro mechanism eliciting pathogenic autoreactive T-cell responses to β2GPI and should be useful in clarifying the pathogenesis of APS.

Original languageEnglish
Pages (from-to)1552-1557
Number of pages6
JournalBlood
Volume105
Issue number4
DOIs
Publication statusPublished - Feb 15 2005
Externally publishedYes

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T-cells
Epitopes
Phospholipids
Glycoproteins
T-Lymphocytes
Processing
Antiphospholipid Syndrome
Amino Acids
Peptides
Antigen Presentation
Dendritic Cells
Bearings (structural)
Antigens
Macrophages
Immune system
HLA-DR Antigens
Autoimmunity
Autoantibodies
Immune System
Blood Cells

ASJC Scopus subject areas

  • Hematology

Cite this

Binding of β2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells. / Kuwana, Masataka; Matsuura, Eiji; Kobayashi, Kazuko; Okazaki, Yuka; Kaburaki, Junichi; Ikeda, Yasuo; Kawakami, Yutaka.

In: Blood, Vol. 105, No. 4, 15.02.2005, p. 1552-1557.

Research output: Contribution to journalArticle

Kuwana, Masataka ; Matsuura, Eiji ; Kobayashi, Kazuko ; Okazaki, Yuka ; Kaburaki, Junichi ; Ikeda, Yasuo ; Kawakami, Yutaka. / Binding of β2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells. In: Blood. 2005 ; Vol. 105, No. 4. pp. 1552-1557.
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