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. We established seven CD4(+) T cell lines reactive with beta(2)GPI peptide. Three of four epitopes for patient-derived T cell lines were p244-264, whereas one T cell line from a control subject also recognized p244-264. Furthermore, there was no tendency for particular HLA class II molecules to present beta(2)GPI peptides. However, cytokine producing patterns were significantly different between T cell lines from patients and those from healthy individuals (p =.028); patients' T cells tend to exhibit higher IL-4 and lower IFN-gamma responses. These T cell lines did not react to beta(2)GPI purified from human plasma. These results indicate that beta(2)GPI-reactive CD4(+) T cells of APS/SLE patients mainly recognize cryptic p244-264 in the context of various HLA class II molecules, and exhibit Th0-Th2-type responses. Our findings may provide a clue to the pathogenesis of APS.
Ito
H
H
Division of Immunogenetics, Department of Neuroscience and Immunology, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
Matsushita
S
S
Tokano
Y
Y
Nishimura
H
H
Tanaka
Y
Y
Fujisao
S
S
Mitsuya
H
H
Hashimoto
H
H
Nishimura
Y
Y
D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000302:isolation & purification; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D019151:Peptide Library; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D053482:beta 2-Glycoprotein I
D001323:Autoantibodies; D001324:Autoantigens; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D006023:Glycoproteins; D006680:HLA Antigens; D000949:Histocompatibility Antigens Class II; D010446:Peptide Fragments; D019151:Peptide Library; D053482:beta 2-Glycoprotein I