Minimal alterations in the HLA-B27-bound peptide repertoire induced upon infection of lymphoid cells withSalmonella typhimurium

Ramos, Manuel; Álvarez, Iñaki; García‐Del‐Portillo, Francisco; Castro, José A. Łópez de

doi:10.1002/1529-0131(200107)44:7<1677::aid-art292>3.0.co;2-u

Cited by 19 publications

(29 citation statements)

References 53 publications

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“…However, we did not find spectral doublets representing S. enterica serovar Typhimurium-derived peptides among the B27-bound peptides isolated from infected C1R-B*2704 cells. This finding is consistent with data reported by Lopez de Castro et al, who used a comparative data approach (41).…”

Section: Discussionsupporting

confidence: 93%

“…Several groups have attempted to identify changes in the B27-bound peptide repertoire after infection with bacteria (5,31,41,43). Most of these studies compared HPLC profiles generated from peptide pools isolated from infected cells with those from uninfected control cells.…”

Section: Discussionmentioning

confidence: 99%

“…Ringrose et al concluded from their comparative data analysis that the presentation of certain host cell peptides may be increased upon bacterial infection (43). A more advanced study was performed by Ramos et al, who used MS analysis to study the peptide contents of all peptide fractions generated by reversed-phase HPLC (41). They found no significant differences between peptide profiles from cells infected with S. enterica serovar Typhimurium and those from control cells, although an as yet uncharacterized low-abundance mass was specifically present in isolates from infected cells.…”

Section: Discussionmentioning

confidence: 99%

“…Until now, for the elucidation of which bacterial peptides are presented by HLA-B27 upon infection, reversed-phase chromatography-fractionated peptide repertoires isolated from B27-expressing cells with or without prior infection were compared. Such comparative data analysis has yielded very limited information so far, although slight differences have been suggested to occur after Salmonella and Shigella infections (5,31,41,43). The comparative approach poses several problems.…”

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Major Histocompatibility Complex Class I Peptide Presentation afterSalmonella entericaSerovar Typhimurium Infection Assessed via Stable Isotope Tagging of the B27-Presented Peptide Repertoire

Ringrose¹,

Meiring²,

Speijer

et al. 2004

Infect Immun

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Reactive arthritis (ReA) induced by infection with several gram-negative bacteria is strongly associated with expression of the major histocompatibility complex class I molecule HLA-B27. It is thought that due to the intracellular lifestyle of ReA-inducing bacteria, bacterial fragments can be presented by HLA-B27. Cytotoxic T cells recognizing such bacterial peptides or other induced host peptides could cross-react with self peptides presented in the joints, giving rise to disease. Studies to analyze the B27 peptide repertoire in relation to infection were severely hampered, as complex peptide profiles obtained from separate infected and noninfected cell preparations had to be compared. For this study, we applied a new approach to examine the effect of Salmonella enterica serovar Typhimurium infection on the B27 peptide repertoire presented by the HLA-B*2704 subtype associated with disease. Firstly, we showed that both host cell and S. enterica serovar Typhimurium proteins can be tagged metabolically with stable-isotope-labeled arginine. We then designed experiments so that either the tagged endogenous or tagged bacterial B*2704-presented peptide repertoires from infected cells could be analyzed by mass spectrometry from single peptide preparations that included uninfected controls. Using this new approach, we found no evidence for significant changes in endogenous B*2704 peptide presentation after infection or for any S. enterica serovar Typhimurium-derived B27-bound peptide. In conclusion, the hypothesis that S. enterica serovar Typhimurium induces changes in B27 peptide presentation could not be supported.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Major Histocompatibility Complex Class I Peptide Presentation afterSalmonella entericaSerovar Typhimurium Infection Assessed via Stable Isotope Tagging of the B27-Presented Peptide Repertoire

Ringrose¹,

Meiring²,

Speijer

et al. 2004

Infect Immun

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“…This hypothesis has prompted extensive searches for B27-restricted CD8 ϩ T cells in patients with these disorders, and extensive characterization of the peptides bound to HLA-B27 that might be presented to these putative T cells (3)(4)(5). To date, these studies have been inconclusive, and no consensus has emerged regarding the role of CD8 T cells in B27-associated disease.…”

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confidence: 99%

CD8αβ T Cells Are Not Essential to the Pathogenesis of Arthritis or Colitis in HLA-B27 Transgenic Rats

May

Dorris

Satumtira

et al. 2003

The Journal of Immunology

161

103

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The class I MHC allele HLA-B27 is highly associated with the human spondyloarthropathies, but the basis for this association remains poorly understood. Transgenic rats with high expression of HLA-B27 develop a multisystem inflammatory disease that includes arthritis and colitis. To investigate whether CD8αβ T cells are needed in this disease, we depleted these cells in B27 transgenic rats before the onset of disease by adult thymectomy plus short-term anti-CD8α mAb treatment. This treatment induced profound, sustained depletion of CD8αβ T cells, but failed to suppress either colitis or arthritis. To address the role of CD8α+β− cells, we studied four additional groups of B27 transgenic rats treated with: 1) continuous anti-CD8α mAb, 2) continuous isotype-matched control mAb, 3) the thymectomy/pulse anti-CD8α regimen, or 4) no treatment. Arthritis occurred in ∼40% of each group, but was most significantly reduced in severity in the anti-CD8α-treated group. In addition to CD8αβ T cells, two sizeable CD8α+β− non-T cell populations were also reduced by the anti-CD8α treatment: 1) NK cells, and 2) a CD4+CD8+CD11b/c+CD161a+CD172a+ monocyte population that became expanded in diseased B27 transgenic rats. These data indicate that HLA-B27-retricted CD8+ T cells are unlikely to serve as effector cells in the transgenic rat model of HLA-B27-associated disease, in opposition to a commonly invoked hypothesis concerning the role of B27 in the spondyloarthropathies. The data also suggest that one or more populations of CD8α+β− non-T cells may play a role in the arthritis that occurs in these rats.

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A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis

Scholz

Mestre-Ferrer

Daura

et al. 2016

Arthritis & Rheumatology

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Objective To evaluate similarity of the peptide repertoires bound to HLA–DR molecules that are differentially associated with rheumatoid arthritis (RA), and to define structural features of the shared peptides. Methods Peptide pools bound to HLA–DRB1*01:01, HLA–DRB1*04:01, and HLA–DRB1*10:01 (RA associated) and those bound to HLA–DRB1*15:01 (non–RA–associated) were purified and analyzed by liquid chromatography (LC) matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry (MS) and LC–ion‐trap MS. Peptide pools from each allotype were compared in terms of size, protein origin, composition, and affinity (both theoretical and experimental with some peptides). Finally, 1 peptide sequenced from DR1, DR4, and DR10, but not from DR15, was modeled in complex with all 4 HLA–DRB1 molecules and HLA–DRB5*01:01. Results A total of 6,309 masses and 962 unique peptide sequences were compared. DR10 shared 29 peptides with DR1, 9 with DR4, and 1 with DR15; DR1 shared 6 peptides with DR4 and 9 with DR15; and DR4 and DR15 shared 4 peptides. The direct identification of peptide ligands indicated that DR1 and DR10 were the most similar molecules regarding the peptides that they could share. The peptides common to these molecules contained a high proportion of Leu at P4 and basic residues at P8 binding core positions. Conclusion The degree of overlap between peptide repertoires associated with different HLA–DR molecules is low. The repertoires associated with DR1 and DR10 have the highest similarity among the molecules analyzed (∼10% overlap). Among the peptides shared between DR1 and DR10, a high proportion contained Leu4 and basic residues at the P8 position of the binding core.

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Minimal alterations in the HLA-B27-bound peptide repertoire induced upon infection of lymphoid cells withSalmonella typhimurium

Cited by 19 publications

References 53 publications

Major Histocompatibility Complex Class I Peptide Presentation afterSalmonella entericaSerovar Typhimurium Infection Assessed via Stable Isotope Tagging of the B27-Presented Peptide Repertoire

Major Histocompatibility Complex Class I Peptide Presentation afterSalmonella entericaSerovar Typhimurium Infection Assessed via Stable Isotope Tagging of the B27-Presented Peptide Repertoire

CD8αβ T Cells Are Not Essential to the Pathogenesis of Arthritis or Colitis in HLA-B27 Transgenic Rats

A Comparative Analysis of the Peptide Repertoires of HLA–DR Molecules Differentially Associated With Rheumatoid Arthritis

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