T cell epitope mapping of the Smith antigen reveals that highly conserved Smith antigen motifs are the dominant target of T cell immunity in systemic lupus erythematosus.
B cell and T cell immunity to the Smith Ag (Sm) is a characteristic feature of systemic lupus erythematosus (SLE). We have shown that T cell immunity against Sm can be detected in SLE patients, and that T and B cell immunity against Sm are linked in vivo. TCR usage by Sm-reactive T cells is highly restricted and characteristic of an Ag-driven immune response. Sm is a well-characterized complex Ag consisting of proteins B1, B2, D1, D2, D3, E, F, and G. A unique feature of all Sm proteins is the presence of homologous motifs, Sm motif 1 and Sm motif 2. We used limiting dilution cloning and synthetic peptide Ags to characterize the human T cell immune response against Sm in seven SLE patients. We sought to determine the precise antigenic peptides recognized, the common features of antigenic structure recognized, and the evolution of the T cell response against Sm. We found there was a highly restricted set of Sm self-peptides recognized by T cells, with three epitopes on Sm-B and two epitopes on Sm-D. We found that T cell immunity against Sm-B and Sm-D was encoded within the highly conserved Sm motif 1 and Sm motif 2, and that immunity against these epitopes appeared stable. The present study supports the concept that T cell immunity to Sm is an Ag-driven immune response directed against a highly restricted set of self-peptides, encoded within Sm motif 1 and Sm motif 2, that is shared among all Sm proteins.
Talken
B L
BL
Division of Immunology and Rheumatology, University of Missouri, Columbia, MO 65212, USA.
Schäfermeyer
K R
KR
Bailey
C W
CW
Lee
D R
DR
Hoffman
R W
RW
D000409:Alanine / Q000378:metabolism; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000276:immunology; D001324:Autoantigens / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D002461:Cell Line, Transformed; D002999:Clone Cells; D017124:Conserved Sequence / Q000276:immunology*; D003430:Cross-Sectional Studies; D018604:Epitope Mapping / Q000379:methods; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000378:metabolism; D005260:Female; D006680:HLA Antigens / Q000378:metabolism; D006801:Humans; D016056:Immunodominant Epitopes / Q000032:analysis* / Q000378:metabolism; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010446:Peptide Fragments / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055517:snRNP Core Proteins
D001324:Autoantigens; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000409:Alanine