Epstein-Barr virus-induced autoimmune responses. I. Immunoglobulin M autoantibodies to proteins mimicking and not mimicking Epstein-Barr virus nuclear antigen-1.
In previous studies of infectious mononucleosis, we found IgM autoantibodies which react with hematopoietic cell antigens. Many of these were inhibited by synthetic glycine/alanine peptides representing the glycine/alanine repeat of Epstein-Barr virus nuclear antigen-1. We have cloned and expressed fragments of genes encoding two of these autoantigens. One gene (p542) encodes a protein containing a glycine-rich 28-mer, which is its chief autoantigenic epitope and which represents a newly identified class of evolutionarily conserved autoepitopes. The other gene (p554) encodes a protein that is not demonstrably cross-reactive with Epstein-Barr virus nuclear antigen-1 or with any other EBV protein, but forms complexes with other proteins. Immunoaffinity-purified anti-p542 and anti-p554 have relatively high binding affinities, as evidenced by inhibition at 10(6)-10(8) M-1, and neither autoantibody showed polyreactivity with other common antigens. The data thus suggest that neither autoantibody is simply an expression of polyclonal B cell activation. We conclude that the two autoantigens stimulate autoantibody synthesis by different mechanisms. One autoantigen shares homology to a viral protein which generates cross-reacting antibodies to the autoantigenic epitope. The other has no recognizable cross-reaction with the infecting pathogen and may become immunogenic through complexing with other proteins.
Vaughan
J H
JH
Department of Medicine, University of California, San Diego, La Jolla 92093-0663.
Valbracht
J R
JR
Nguyen
M D
MD
Handley
H H
HH
Smith
R S
RS
Patrick
K
K
Rhodes
G H
GH
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000276:immunology*; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D007244:Infectious Mononucleosis / Q000276:immunology*; D007962:Leukocytes; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000276:immunology
D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D004268:DNA-Binding Proteins; D000939:Epitopes; D019309:Epstein-Barr Virus Nuclear Antigens; D007075:Immunoglobulin M; D011993:Recombinant Fusion Proteins