Beta2-glycoprotein I: antiphospholipid syndrome and T-cell reactivity.

Abstract

There is increasing evidence showing that recurrent thrombosis and intrauterine fetal loss in antiphospholipid syndrome (APS) are attributable to antiphospholipid (aPL) antibodies. We have recently identified autoreactive CD4+ T cells to beta2-glycoprotein I (beta2GPI) that promote production of pathogenic antiphospholipid antibodies. beta2GPI-specific CD4+ T cells preferentially recognize the antigenic peptide containing the major phospholipid (PL)-binding site in the context of DR53. T-cell helper activity that stimulates B cells to produce IgG anti-beta2GPI antibodies is mediated through IL-6 and CD40-CD154 interaction. beta2GPI-specific T cells respond to reduced beta2GPI and recombinant beta2GPI fragments produced in a bacterial expression system but not to native beta2GPI, indicating that the epitopes recognized by beta2GPI-specific T cells are 'cryptic' determinants, which are generated at a subthreshold level by the processing of native beta2GPI under normal circumstances. Although beta2GPI-specific T cells are detected in both APS patients and healthy individuals, these autoreactive T cells are activated in vivo in APS patients but not in healthy individuals. These findings indicate activation of beta2GPI-specific T cells and subsequent production of pathogenic anti-beta2GPI antibodies can be induced by the exposure of such T cells to cryptic peptides of beta2GPI efficiently presented by functional antigen-presenting cells (APC). Delineating the mechanisms that induce the efficient processing and presentation of cryptic determinants of beta2GPI as a consequence of antigen processing would clarify the etiology that initiates the autoantibody response in APS.

• Authors: Masataka Kuwana
• Journal: Thrombosis research (Thromb Res) Vol. 114 Issue 5-6 Pg. 347-55 ( 2004) ISSN: 0049-3848 [Print] United States
• PMID: 15507264 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antibodies, Antiphospholipid
• Autoantibodies
• CD40 Antigens
• Glycoproteins
• HLA-DR Antigens
• HLA-DR53
• HLA-DRB4 Chains
• Interleukin-6
• Peptides
• beta 2-Glycoprotein I
• CD40 Ligand

Topics

• Amino Acid Motifs
• Antibodies, Antiphospholipid (chemistry)
• Antigen Presentation
• Antiphospholipid Syndrome (metabolism, pathology)
• Autoantibodies (chemistry)
• Binding Sites
• CD4-Positive T-Lymphocytes (metabolism)
• CD40 Antigens (biosynthesis)
• CD40 Ligand (biosynthesis)
• Glycoproteins (metabolism, physiology)
• HLA-DR Antigens (chemistry)
• HLA-DRB4 Chains
• Humans
• Interleukin-6 (metabolism)
• Lupus Erythematosus, Systemic (metabolism)
• Models, Biological
• Peptides (chemistry)
• beta 2-Glycoprotein I