B cell epitope on the U1 snRNP-C autoantigen contains a sequence similar to that of the herpes simplex virus protein.
The mechanism of autoantibody production in autoimmune diseases is not well understood. In the present study we performed the B cell epitope mapping of the U1 small nuclear ribonucleoprotein (snRNP)-C, one of the target molecules of anti-nRNP autoantibody to investigate how B cells respond to the autoantigen. After cloning and expression of a full length complementary DNA (cDNA) encoding the U1-C protein, several truncated mutants of the cDNA were constructed and expressed in E. coli. Although a few epitopes were distributed on the whole molecule, all anti-C protein antibody-positive patients' sera tested recognized the region between amino acid residues 102 and 125 of the coding sequence. This universal epitope region contains an amino acid sequence similar to that of the herpes simplex virus type 1 ICP4 protein. The peptides representing each molecule were cross-reactive to each other. In addition this region cross-reacted to the B/B' protein. These observations suggest that molecular mimicry might be involved in the initiation of autoantibody production, followed by cross-reactive events between the autoantigens and by antigen-driven mechanisms to generate more complicated autoantibody patterns against the U1 snRNP complexes.
Misaki
Y
Y
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Japan.
Yamamoto
K
K
Yanagi
K
K
Miura
H
H
Ichijo
H
H
Kato
T
T
Mato
T
T
Welling-Wester
S
S
Nishioka
K
K
Ito
K
K
D000595:Amino Acid Sequence; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003001:Cloning, Molecular; D003429:Cross Reactions; D000939:Epitopes / Q000032:analysis*; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000235:genetics / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D018139:Simplexvirus / Q000276:immunology*; D054334:Viral Regulatory and Accessory Proteins / Q000276:immunology*; D055517:snRNP Core Proteins
D001324:Autoantigens; D000939:Epitopes; D017874:Immediate-Early Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D054334:Viral Regulatory and Accessory Proteins; C048925:herpes simplex virus, type 1 protein ICP4; D055517:snRNP Core Proteins