Evidence map›Paper›PMID 24434326›Full record

ArticleThe Indian journal of medical research2013

Lipidated promiscuous peptide augments the expression of MHC-II molecules on dendritic cells and activates T cells.

Uthaman Gowthaman, Pradeep K Rai, Weiguang Zeng, David C Jackson, Javed N Agrewala

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Article in The Indian journal of medical research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Uthaman Gowthaman
Pradeep K Rai
Weiguang Zeng
David C Jackson
Javed N AgrewalaCSIR-Institute of Microbial Technology, Chandigarh, India.
Institute of Microbial Technology · INUniversity of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND &

objectivesIn spite of the fact that BCG is the most widely used vaccine, tuberculosis (TB) continues to be a major killer disease in TB-endemic regions. Recently, many emerging evidences from the published literature indicate the role of environmental mycobacteria in blocking the processing and presentation of BCG antigens and thereby impairing with suboptimal generation of protective T cells. To surmount this problem associated with BCG, we constructed a novel lipopeptide (L91) by conjugating a promiscuous peptide consisting of CD4 + T-helper epitope of sequence of 91-110 of 16 kDa antigen of Mycobacterium tuberculosis to Pam2Cys, an agonist of Toll-like receptor-2.

methodsMice were immunized subcutaneously with 20 nmol of L91, followed by a booster with 10 nmol, after an interval of 21 days of primary immunization. Animals were sacrificed after seven days of post-booster immunization. L91 induced immune response was characterized by the expression of MHC-II and CD74 on the surface of dendritic cells (DCs) by flowcytometry. Cytokines (IL-4, IL-10, IFN-γ) secretion and anti-peptide antibodies were measured by ELISA.

resultsSelf-adjuvanting lipopeptide vaccine (L91) was directly bound to MHC-II molecules and without requiring extensive processing for its presentation to T cells. It stimulated and activated dendritic cells and augmented the expression of MHC-II molecules. Further, it activated effector CD4 T cells to mainly secrete interferon (IFN)-γ but not interleukin (IL)-4 and IL-10. L91 did not elicit anti-peptide antibodies. INTERPRETATION &

conclusionsThe findings suggest that L91 evokes maturation and upregulation of MHC class II molecules and promotes better antigen presentation and, therefore, optimum activation of T cells. L91 mainly induces effector Th1 cells, as evidenced by predominant release of IFN-γ, consequently can mount favourable immune response against M. tuberculosis . As L91 does not provoke the generation of anti-peptide antibodies, there is no fear of the efficacy of the vaccine being neutralized by pre-existing anti-mycobacterial antibodies in TB-endemic population. In conclusion, L91 may be considered as a future potential candidate vaccine against TB.

Indexed as

AnimalsAntigen PresentationDendritic CellsGene Expression RegulationGenes, MHC Class IIHumansInterferon-gammaInterleukin-4LipidsLymphocyte ActivationMiceMycobacterium bovisMycobacterium tuberculosisPeptidesTuberculosisInterferon-gammaInterleukin-4LipidsPeptides

Identifiers

PMID24434326
PMCPMC3928704
OpenAlexW2171461837

What OpenQuestion holds

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LicenceCC BY-NC-SA
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.