Alteration of HLA-B27 Peptide Presentation after Infection of Transfected Murine L Cells byShigella flexneri

Abstract

Shigella flexneri is a triggering agent for reactive arthritis in HLA-B27-susceptible individuals. Considering the intracellular multiplication of bacteria, it seems likely that bacterial peptides may be presented by the major histocompatibility complex (MHC) class I pathway. To examine this hypothesis, we infected HLA-B*2705- and/or human β2-microglobulin-transfected murine L-cell lines with M90T, an invasive strain of S. flexneri. Bacterial infection induced no detectable modifications in the biosynthesis and expression level of HLA-B27, as assessed by immunoprecipitation, Northern blot analysis, and flow cytometry. Using confocal microscopy, we observed that bacterial infection induced a clustering of HLA-B27 molecules during macropinocytosis and before bacterial dissemination from cell to cell. Peptides naturally bound to HLA-B27 molecules were acid eluted from infected cells and separated by high-performance liquid chromatography. Major differences were observed in high-performance liquid chromatography profiles and in the nature of peptides presented following bacterial infection. Although most of the antigens presented were not accessed by Edman degradation, we obtained two sequences partially homologous to bacterial proteins. These peptides lacked the major HLA-B27 peptide anchor (Arg) at position 2, and one had an unusual length of 14 amino acids. These data suggest that alterations in the peptide presentation by HLA-B27 occur during infection, which could be relevant to the pathogenesis of HLA-B27-related arthritis.

Infection with Salmonella typhimurium has no effect on the composition and cleavage specificity of the 20S proteasome in human lymphoid cells

“…15 Changes in the B27-bound peptide repertoire were also reported in L cells infected with Shigella flexneri. 16 In contrast, in the lymphoid cell line C1R, the HLA-B27-bound peptide repertoires from S. typhimurium-infected and non-infected cells are very similar. 1,17,18 Nevertheless, B27-restricted bacteria-specific CTLs isolated from synovial fluid of ReA patients killed Salmonella-infected HLA-B27-C1R targets, 19 suggesting that small amounts of bacterial peptides were presented by HLA-B27 on these cells.…”

“…It has been reported that infection of HeLa cells by S. typhimurium results in an increase of the inducible subunit β 1 i, and concomitant changes in the HLA‐B27‐bound peptide repertoire 15 . Changes in the B27‐bound peptide repertoire were also reported in L cells infected with Shigella flexneri 16 . In contrast, in the lymphoid cell line C1R, the HLA‐B27‐bound peptide repertoires from S. typhimurium ‐infected and non‐infected cells are very similar 1,17 , 18 .…”

Enterobacterial infection modulates major histocompatibility complex class I expression on mononuclear cells

“…It might be caused by changes in the peptide repertoire presented on the cell surface 22 . In another in vitro study, Shigella infection did not down‐regulate the expression of HLA‐B27 but induced clustering of HLA‐B27 molecules during macropinosytosis and alterations in the peptide presentation by HLA‐B27 23 …”