Endogenous Processing and Presentation of T-cell Epitopes from Chlamydia trachomatis with Relevance in HLA-B27-associated Reactive Arthritis

Cragnolini, Juan J.; García-Medel, Noel; Castro, José A. Łópez de

doi:10.1074/mcp.m900107-mcp200

Cited by 22 publications

(21 citation statements)

References 45 publications

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“…ReA is strongly correlated with the expression of a particular MHC class I allele, HLA-B27 (47)(48)(49). Animal models have shown that chlamydia-reactive CD8 ϩ T cells can recognize self-peptides bound to HLA-B27 (50-52).…”

Section: Discussionmentioning

confidence: 99%

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

et al. 2016

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The direct major histocompatibility complex (MHC) class I antigen presentation pathway ensures intracellular peptides are displayed at the cellular surface for recognition of infected or transformed cells by CD8 ؉ cytotoxic T lymphocytes. Chlamydia spp. are obligate intracellular bacteria and, as such, should be targeted by CD8 ؉ T cells. It is likely that Chlamydia spp. have evolved mechanisms to avoid the CD8 ؉ killer T cell responses by interfering with MHC class I antigen presentation. Using a model system of self-peptide presentation which allows for posttranslational control of the model protein's stability, we tested the ability of various Chlamydia species to alter direct MHC class I antigen presentation. Infection of the JY lymphoblastoid cell line limited the accumulation of a model host protein and increased presentation of the model-protein-derived peptides. Enhanced selfpeptide presentation was detected only when presentation was restricted to defective ribosomal products, or DRiPs, and total MHC class I levels remained unaltered. Skewed antigen presentation was dependent on a bacterial synthesized component, as evidenced by reversal of the observed phenotype upon preventing bacterial transcription, translation, and the inhibition of bacterial lipooligosaccharide synthesis. These data suggest that Chlamydia spp. have evolved to alter the host antigen presentation machinery to favor presentation of defective and rapidly degraded forms of self-antigen, possibly as a mechanism to diminish the presentation of peptides derived from bacterial proteins.

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Section: Discussionmentioning

confidence: 99%

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

et al. 2016

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“…Besides, the recent reports that certain cytokine profiles of anti-chlamydial immune effectors, are critical for preventing immunopathology [10,11] may offer appropriate screening methods for antigen immuno-toxicity or potential for inducing protective immunity; accordingly, the induction of an appropriate immune profile that include IFN-γ or an inappropriate cytokine profile, such as the absence of IFN-γ or a predominantly Th2 or T17 response [10][11][12][13], and presence of potentially pathogenic properties in the antigen [14][15][16][17][18] are promising vaccine antigen screening and discovery approaches. In addition, the profile of cytokines and immune effectors of an anti-chlamydial immune response in infections with and without pathologic complications may also provide a useful molecular and immunological biomarker for predicting chlamydial pathologies.…”

Section: Trachomatis Genital Infection Is the Most Common Bacterialmentioning

confidence: 99%

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

Igietseme¹

2017

CIIT

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The simultaneous induction of protective and immunopathogenic responses during genital C. trachomatis infection is proposed to respectively confer partial immunity and at least partly drive the complications such as pelvic inflammatory disease and tubal factor infertility. T cell-mediated immune response is crucial for chlamydial immunity in experimental animal models and in humans. However, the levels of T cell-derived cytokines in human specimens such as serum or mucosal tissue fluids can be influenced by several factors in addition to the incident infection. Therefore, it is uncertain whether T cell cytokine levels in biological fluids can predict infections that lead to complications, and can be used as reliable biomarkers of chlamydial disease complications, such as tubal factor infertility. Using a reliable murine model of chlamydiainduced infertility, we tested the hypothesis that the anti-chlamydial T cell immune effectors induced during infections that produce complications are qualitatively or quantitatively distinct from non-complicated infections. The results revealed that infected infertile mice exhibited lower systemic anti-chlamydial total IgG levels than animals with comparable microbiological shedding of chlamydiae but protected from infertility by treatment with the pan-caspase inhibitor Z-VAD-FMK. Interestingly, infected fertile mice showed greater Th1-type cytokines, mostly TNF-α, IFN-γ and IL-17 than infertile animals, while levels of the Th2-type cytokines, IL-5 and IL-10 were higher in infected infertile mice than fertile mice. These profiles of systemic cytokine levels in mice are corroborated by clinical findings demonstrating that chlamydial infection with tubal pathologies elicited a predominantly Th2 immune response. Thus, antigen-specific T cell cytokine response may distinguish infections leading to immunity versus sequelae, providing a useful prognostic biomarker and as a guide for vaccine design and evaluation.

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“…Posteriormente, se expresó un fragmento proteico que incluía parte de la secuencia homóloga a B27 de esta ADN-primasa bacteriana en líneas celulares B27-positivas, probando que la construcción proteica era procesada y presentada "in vivo" por B*27:05 16 . Además, mediante inmunoproteómica comparada, se demostró que un péptido bacteriano homólogo al ligando propio de B*27 era procesado y presentado endógena-mente, demostrando la existencia de mimetismo molecular 17 . Sin embargo, a pesar de todas estas evidencias, aún no se ha podido constatar la existencia de péptidos artritogénicos.…”

Section: Hla-b27unclassified

Genética, HLA-B27 y espondilitis anquilosante: 40 años

Castro‐Santos¹,

Gutiérrez²,

Díaz‐Peña³

2014

Rev. méd. Chile

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Genetics of ankylosing spondylitis Ankylosing spondylitis (AS) is a prototypical inflammatory disease of the locomotor system affecting axial skeleton. It is part of the general group of spondyloarthopathies (SpAEpidemiología L a espondilitis anquilosante (EA) es el prototipo de las enfermedades inflamatorias del aparato locomotor que afectan al esqueleto axial y que se engloban bajo el término de espondiloartropatías (SpA). La EA es una patología de etiología desconocida cuyas principales alteraciones se producen en las zonas de inserción de ligamentos y tendones en el hueso (entesis), en la membrana sinovial y en el cartílago articular. Se considera que afecta más frecuentemente a los varones (en una relación de 3:1 respecto de las mujeres) y aparece normalmente entre los 20-30 años de vida. La prevalencia de la EA varía según zona geográfica, etnia, factores genéticos y ambientales, persistiendo aún muchos factores que se desconocen 1 . La investigación de la EA ha dado un papel fundamental al antígeno de histocompatibilidad HLA-B27, molécula capaz de acoplar un péptido en su interior que permite la posterior activación del linfocito T, y por tanto, imprescindible para el reconocimiento de lo propio y lo ajeno por parte del sistema inmune. Las diferencias en la prevalencia de HLA-B27 explican la mayor parte de la variación en la prevalencia de la EA vista en todo el mundo 2,3 . Presentar en nuestro organismo este antígeno supone una probabilidad de 1-2% de padecer EA, aunque aumenta hasta el 10-20% si, además de ser B27-positivo, existe un familiar de primer grado que ya padece la enfermedad. Lo interesante es que alrededor del 80-95% de las personas caucasoides con EA presentan positividad para HLA B27, por lo que establecer una relación entre su presencia y el desarrollo de la enfermedad ha sido el objetivo de numerosas investigaciones. En otros grupos étnicos, la relación con el HLA-B27 no es tan estrecha 1,4,5 . De este modo, sabemos que la presencia de HLA-B27 no significa que una persona padezca o vaya a padecer EA, pero en el caso de existir determinados síntomas, variaciones en parámetros bioquímicos y ciertos signos radiológicos, existiría un indicador que puede contribuir al diagnóstico definitivo, e incluso que podría ser útil en el diagnóstico diferencial de otras patologías.

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Endogenous Processing and Presentation of T-cell Epitopes from Chlamydia trachomatis with Relevance in HLA-B27-associated Reactive Arthritis

Cited by 22 publications

References 45 publications

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

Enhanced Direct Major Histocompatibility Complex Class I Self-Antigen Presentation Induced by Chlamydia Infection

Profile of Anti-Chlamydia Immune Responses in Complicated (Infertile) and Non-complicated (Fertile) Genital Infections

Genética, HLA-B27 y espondilitis anquilosante: 40 años

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