6 research outputs found

    Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222 by combinatorial peptide library screening

    Get PDF
    The CD8 T cell response to the HLA-A2-restricted epitope LLWNGPMAV (LLW) of the non-structural protein 4b of Yellow Fever Virus (YFV) is remarkably immunodominant, highly prevalent and powerful in YFV-vaccinated humans. Here we used a combinatorial peptide library screening in the context of an A2/LLW-specific CD8 T cell clone to identify a superagonist that features a methionine to isoleucine substitution at position 7. Based on in silico modeling, the functional enhancement of this LLW-7I mutation was associated with alterations in the structural dynamics of the peptide in the major histocompatibility complex (pMHC) binding with the T cell receptor (TCR). While the TCR off-rate of LLW-7I pMHC is comparable to the wild type peptide, the rigidity of the 7I peptide seems to confer less entropy loss upon TCR binding. This LLW-7I superagonist is an example of improved functionality in human CD8 T cells associated with optimized ligand rigidity for TCR binding and not with changes in TCR:pMHC off-rate kinetics

    Adjuvant Effect of Leishmania major Promastigotes on the Immune Response of Mice to Ovalbumin

    Get PDF
    ABSTRACT The immune responses of mice immunized with ovalbumin (OVA) together with killed L. major (KLM) promastigotes as adjuvant were studied. Three doses (5 × 10 7 , 1 × 10 8 and 2 × 10 8 ) of KLM combined with OVA (100 µg) were injected into the groups of C57BL/6 mice. BCG and complete Freund's adjuvant (CFA) were used as control adjuvants. Lymphocyte proliferation and antibody titers were determined, and IFN-γ and IL-4 were measured in the supernatants of lymph node cell cultures. Results showed that immunization using OVA mixed with KLM enhanced the in vitro proliferative response of T-cells to the antigen and resulted in the production of increased levels of IFN-γ (2800-3700 pg/ml) relative to the mice injected with OVA alone (1750 pg/ml). In the mice receiving OVA + 5 × 10 7 KLM, the production of IL-4 remained lower (18, 20 pg/ml) than OVA alone (105, 109 pg/ml) and almost was similar to that of observed in mice inoculated with OVA + BCG, leading to high IFN-γ/IL-4 ratios. Using higher doses of KLM (1 × 10 8 ), the IL-4 responses were of the same magnitude as or higher than the responses of mice inoculated with OVA + CFA. Antibody titers to OVA were also strongly boosted at the highest KLM dose. These findings indicate that KLM may function as an adjuvant, and its dose plays a role in the eventual outcome of the response. Inoculation of the mice with a low dose of KLM (5 × 10 7 ) tends to promote a Th1-type response. Iran. Biomed. J. 6 (4): 123-128, 200

    Identification of a superagonist variant of the immunodominant Yellow fever virus epitope NS4b214-222 by combinatorial peptide library screening

    Get PDF
    The CD8 T cell response to the HLA-A2-restricted epitope LLWNGPMAV (LLW) of the non-structural protein 4b of Yellow Fever Virus (YFV) is remarkably immunodominant, highly prevalent and powerful in YFV-vaccinated humans. Here we used a combinatorial peptide library screening in the context of an A2/LLW-specific CD8 T cell clone to identify a superagonist that features a methionine to isoleucine substitution at position 7. Based on in silico modeling, the functional enhancement of this LLW-7I mutation was associated with alterations in the structural dynamics of the peptide in the major histocompatibility complex (pMHC) binding with the T cell receptor (TCR). While the TCR off-rate of LLW-7I pMHC is comparable to the wild type peptide, the rigidity of the 7I peptide seems to confer less entropy loss upon TCR binding. This LLW-7I superagonist is an example of improved functionality in human CD8 T cells associated with optimized ligand rigidity for TCR binding and not with changes in TCR:pMHC off-rate kinetics

    Comment faciliter la réinsertion socioprofessionnelle du patient neurolésé ::outils pour le praticien

    No full text
    Les jeunes en transition de l’enfance à l’âge adulte présentant une maladie neurodéveloppementale sont une population spécialement vulnérable. Le suivi de leurs problèmes de santé et leur insertion socioprofessionnelle représentent un véritable défi. Au CHUV, à Lausanne, une consultation de transition entre les neurorééducateurs pédiatriques et adultes a été créée en 2006 ainsi qu’un projet pilote suisse de réinsertion socioprofessionnelle en collaboration avec l’Office de l’assurance invalidité pour le canton de Vaud. Le résultat de ce projet pilote, qui peut être utilisé comme modèle pour tous les patients neurolésés, est rapporté ici avec comme objectif d’informer le médecin traitant et de lui permettre d’utiliser les outils de cette prestation holistique afin d’optimiser la durée et la qualité de la réinsertion

    Sciatica in the female patient: anatomical considerations, aetiology and review of the literature

    No full text
    The principal author was confronted few years ago with the case of a 38-year-old woman with a 5-month history of ill-defined L5 sciatic pain that was referred to an orthopaedic department for investigation and eventual surgical treatment for what was suspected to be herniated disc-related sciatica. Removal of her enlarged uterus found unexpectedly close to the sacroiliac joint upon lumbar MRI abolished her symptoms. Review of the literature showed that the lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Physiological processes in the female patient and gynaecological diseases may be the source of sciatica, often not readily searched for, leading to fruitless investigations and surgical treatments. The aim of the paper is to highlight gynaecological and obstetrical causes of sciatica and sciatica-like symptoms. To prevent unproductive expenses and morbidity, a thorough gynaecological examination should be done even though neurological examination may be suggestive of a herniated intervertebral disc, and the cyclic pattern of pain related to menses should be routinely asked for
    corecore