Analysis of T cell responses to the beta 2-glycoprotein I-derived peptide library in patients with anti-beta 2-glycoprotein I antibody-associated autoimmunity.

Antiphospholipid syndrome (APS) is an autoimmune disease that accompanies anti-phospholipid antibodies measured as either anti-cardiolipin antibodies (aCL) or lupus anticoagulant. beta(2)-glycoprotein I (beta(2)GPI) is the most common and apparently the best-characterized antigenic target for aCL. To investigate T-cell responses to beta(2)GPI, we stimulated PBMC of 18 APS or systemic lupus erythematosus (SLE) patients carrying anti-beta(2)GPI and 10 healthy controls, using a peptide library covering the beta(2)GPI sequence.

Peptide-based molecular analyses of HLA class II-associated susceptibility to autoimmune diseases.

Recent advances in knowledge of crystal structures of MHC class II molecules has advanced understanding of the molecular basis for interactions between peptides and HLA class II molecules. Polymorphism of HLA class II molecules influences structures of peptides bound to HLA class II molecules. To better understand mechanisms related to particular HLA class II alleles and autoimmune diseases, it is important to identify self-peptides presented by disease-susceptible HLA class II molecules and triggering disease-causative autoreactive T cells.

Th1/Th2 balance alteration in the clinical course of a patient with pure red cell aplasia and thymoma.

Peripheral T helper subsets in a patient with acquired pure red cell aplasia (PRCA) and thymoma were analysed by flow cytometry. Thymectomy resulted in a transient but definite improvement in anaemia. A continuous remission was attained by cyclosporin A (CsA) therapy.

Molecular mechanisms underlying HLA-DR-associated susceptibility to autoimmunity.

We analyzed structural motifs of peptides bound to HLA-DR4 (DRB1*0405 and DRB1*0406) and DR9 (DRB1*0901) and found that: (a) AxxBxC motif where A, B, and C are hydrophobic, hydrophobic, and neutral, respectively, is important for binding to DR4; (b) Gln (Q) or Ser at position C allow high-affinity binding specific to DRB1*0406 which is strongly associated with insulin autoimmune syndrome; (c) among human insulin-derived peptide fragments, the TSICSLYQLE of the human insulin alpha chain, which is exposed only under reducing conditions, has the highest affinity specific to DRB1*0406 by binding with the IxxLxQ motif; (d) a short-term human insulin-specific T cell line recognizes a peptide fragment containing the IxxLxQ motif as a major T cell epitope; and (e) in the AxxB motif, where A and B need to be hydrophobic for binding to DR9, neutral Ser is exceptionally allowed at position B. The implications of our results are discussed in light of the HLA-DR4-associated susceptibility to insulin autoimmune syndrome and HLA-DR9-associated susceptibility to juvenile-onset myasthenia gravis and systemic lupus erythematosus with antiphospholipid syndrome, in particular T cell responses to autoantigens.