Diverse humoral autoimmunity to the ribosomal P proteins in systemic lupus erythematosus and hepatitis C virus infection.
Autoantibodies to the three ribosomal P proteins (Rib-P) are specifically found in 10% to 40% of systemic lupus erythematosus (SLE) patients. Most anti-Rib-P autoantibodies bind to a C-terminal epitope shared by all three Rib-P proteins P0, P1 and P2. In the present study, we shed more light on the humoral autoimmune response to the Rib-P antigen as it occurs in autoimmunity and infectious disease. In a mutational analysis of the major C-terminal epitope, we verified the key role of phenylalanine residues Phe ( 111 ) and Phe ( 114 ) for binding of most anti-Rib-P serum autoantibodies present in SLE sera (n = 28). By nuclear magnetic resonance (NMR) investigation of a peptide comprising the C-terminal 22 amino acids, we observed hallmarks for alpha-helical secondary structure of the Rib-P epitope core (GFGLFD). Based on NMR data and on SPOT epitope analysis, we propose a structural model of the Rib-P major epitope, which displays Phe ( 111 ) and Phe ( 114 ) on one side of the helix. Apart from that, two sera from the hepatitis C virus (HCV) control group (n = 68) were found to contain antibodies specific for P2, but not for the other Rib-P proteins. Using a SPOT peptide array scanning the P2 amino acid sequence, we identified reactivity with two distinct epitopes (residues 21-35 and 41-55 of Rib-P2) shared by both HCV sera. We conclude that anti-Rib-P autoreactivity occurs in SLE, Chagas' disease (CD) and-as firstly described here-during HCV infection. Anti-Rib-P reactivity in SLE sera primarily depends on Phe ( 111 ) and Phe ( 114 ) of the alpha-helical C-terminal epitope. In contrast, anti-Rib-P autoantibodies in HCV infection mainly recognize epitopes within the N-terminal half of ribosomal P2.
University of Heidelberg, Heidelberg, Germany.
K
K
Kessenbrock
M J
MJ
Fritzler
M
M
Groves
P
P
Eissfeller
C A
CA
von Mühlen
P
P
Höpfl
M
M
Mahler
D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012269:Ribosomal Proteins / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D012269:Ribosomal Proteins