Positive selection in autoimmunity: abnormal immune responses to a bacterial dnaJ antigenic determinant in patients with early rheumatoid arthritis.
A novel 'multistep molecular mimicry' mechanism for induction of rheumatoid arthritis (RA) by bacterial antigens that activate T lymphocytes previously 'educated' by peptides derived from a class of human histocompatibility antigens is reported here. These antigens have the amino acid sequence QKRAA, which is also present on the Escherichia coli heat-shock protein dnaJ. Synovial fluid cells of early RA patients have strong immune responses to the bacterial antigen, but cells from normal subjects or controls with other autoimmune diseases do not. The activated T cells may cross-react with autologous dnaJ heat-shock proteins that are expressed at synovial sites of inflammation. Our findings may have direct relevance to new strategies for the immune therapy of RA.
Albani
S
S
Department of Medicine, University of California, San Diego, La Jolla 92093-0663, USA.
Keystone
E C
EC
Nelson
J L
JL
Ollier
W E
WE
La Cava
A
A
Montemayor
A C
AC
Weber
D A
DA
Montecucco
C
C
Martini
A
A
Carson
D A
DA
D000595:Amino Acid Sequence; D000918:Antibody Specificity; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000494:pharmacology*; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D005260:Female; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000494:pharmacology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013997:Time Factors
D001426:Bacterial Proteins; C494635:DnaJ protein, E coli; D029968:Escherichia coli Proteins; D006680:HLA Antigens; D050956:HSP40 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D010455:Peptides