ME1 epitope of HLA-B27 confers class I-mediated modulation of gram-negative bacterial invasion.
We have previously demonstrated that the presence of the MHC class I molecule, HLA-B27, on the surface of transfected fibroblasts differentially alters Gram-negative bacterial invasion as compared with class I alleles that are not implicated in the seronegative spondyloarthropathies. We have now extended this analysis to show that fibroblasts transfected with HLA-B7, a cross-reactive allele with HLA-B27, also demonstrate a similar altered bacterial invasion phenotype. The decrease in the ability of the bacteria to penetrate the HLA-B27 and HLA-B7 transfectants is an invasion-mediated event, as demonstrated by differential invasion events using Escherichia coli transfected with the inv gene of Yersinia enterocolitica. The lysine at position 70, although unique to the HLA-B27 subtypes, is shown to be not involved in mediating the decrease in invasion. However, the ME1 epitope is the critical factor in determining allele-specific alteration in invasion on the basis of the following: 1) ME1 mAb preincubation reverses the decrease; 2) ME1-binding alleles act like HLA-B27; 3) a class I allele that is intermediate in ME1 binding (HLA-B14) also demonstrates a relative decrease in invasion; and 4) mutation at residue 67 (C-->Y) in HLA-B27, which eliminates the ME1 epitope, normalizes the decreased invasion seen in the native HLA-B27-transfected cells. Thus, the ME1 epitope relates to the disease susceptibility for reactive arthritis that is conferred by both HLA-B27 and cross-reactive group Ags.
Kapasi
K
K
Toronto Hospital Research Institute, University of Toronto, Ontario, Canada.
Inman
R D
RD
D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000502:physiology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D015235:HLA-B Antigens / Q000502:physiology; D059909:HLA-B14 Antigen; D015796:HLA-B27 Antigen / Q000276:immunology / Q000502:physiology*; D006801:Humans; D014162:Transfection
D000939:Epitopes; D015235:HLA-B Antigens; D059909:HLA-B14 Antigen; D015796:HLA-B27 Antigen