Molecular mimickry between HLA B27 and Yersinia, Salmonella, Shigella and Klebsiella within the same region of HLA alpha 1-helix.
Two new examples of amino acid homology between HLA B27 and microbes triggering HLA B27-associated diseases are described. An outer membrane protein YadA (Yersinia adhesin, previously called Yop1) of Yersinia enterocolitica and Y. pseudotuberculosis shares a linear tetrapeptide with HLA B27. A cationic outer membrane protein OmpH of Salmonella typhimurium shares homology with five amino acids of HLA B27 in a non-linear fashion. The four amino acids of YadA are also notably included in the hexapeptide identical between Klebsiella pneumoniae nitrogenase and HLA B27, and three of them occur in the pentapeptide shared by a Shigella flexneri protein and HLA B27. Antibodies against synthetic peptides including HLA B27 homologues sequences of YadA and OmpH were observed in one-third of the patients with HLA B27 associated diseases. Antibodies were directed against a flanking sequence next to the amino acid sequences shared by arthritis-triggering microbes and HLA B27. The area of identity in each example of this molecular mimicry (Yersinia, Salmonella, Shigella and Klebsiella) is located in the same place on the HLA B27 molecule: between amino acids 70 to 78 in the variable region of alpha 1-helix. This area of HLA B27 molecule includes sites predicted to be important for binding processed antigens.
Lahesmaa
R
R
Department of Medical Microbiology, Turku University, Finland.
Skurnik
M
M
Vaara
M
M
Leirisalo-Repo
M
M
Nissilä
M
M
Granfors
K
K
Toivanen
P
P
D018829:Adhesins, Bacterial; D000328:Adult; D000595:Amino Acid Sequence; D001170:Arthritis, Infectious / Q000276:immunology; D016918:Arthritis, Reactive / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology; D005260:Female; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007124:Immunoenzyme Techniques; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007711:Klebsiella pneumoniae / Q000235:genetics* / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D012475:Salmonella / Q000235:genetics* / Q000276:immunology; D012480:Salmonella Infections / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid; D012763:Shigella flexneri / Q000235:genetics* / Q000276:immunology; D013167:Spondylitis, Ankylosing / Q000276:immunology; D015008:Yersinia enterocolitica / Q000235:genetics* / Q000276:immunology
D018829:Adhesins, Bacterial; D001425:Bacterial Outer Membrane Proteins; D015796:HLA-B27 Antigen; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C064832:YadA protein, Yersinia; C067128:ompH protein, bacteria