Polimorfismos del sistema HLA (loci A*, B* y DRB1*) en población colombiana

Ossa, Humberto; Manrique, A.; Quintanilla, Sonia; Peña, A

doi:10.22490/24629448.369

Cited by 7 publications

(1 citation statement)

References 12 publications

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“…Some 15-mer peptide sequences were selected by the following criteria: i) sequences with %Rank≥2 (strong binders) for at least two out of three prediction tools for more than one HLA-DR allele evaluated; ii) identical or similar sequences (synonym substitutions) between L. panamensis, L. braziliensis, and L. major species; and iii) sequences different from their human homolog when applicable. HLA-DR alleles taken in these predictions were based on studies of the most frequent alleles in the Colombian population (Trachtenberg et al, 1996;Correa et al, 2002;Reyes et al, 2007;Arias-Murillo et al, 2010;Ávila-Portillo et al, 2010;Yunis et al, 2013).…”

Section: In Silico Analysis For T Epitopesmentioning

confidence: 99%

Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

Flórez

Rodríguez

Cabrera³

et al. 2021

Front. Cell. Infect. Microbiol.

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Vaccines are one of the most effective strategies to fight infectious diseases. Reverse vaccinology strategies provide tools to perform in silico screening and a rational selection of potential candidates on a large scale before reaching in vitro and in vivo evaluations. Leishmania infection in humans produces clinical symptoms in some individuals, while another part of the population is naturally resistant (asymptomatic course) to the disease, and therefore their immune response controls parasite replication. By the identification of epitopes directly in humans, especially in those resistant to the disease, the probabilities of designing an effective vaccine are higher. The aim of this work was the identification of Leishmania epitopes in resistant humans. To achieve that, 11 peptide sequences (from Leishmania antigenic proteins) were selected using epitope prediction tools, and then, peripheral blood mononuclear cells (PBMCs) were isolated from human volunteers who were previously divided into four clinical groups: susceptible, resistant, exposed and not exposed to the parasite. The induction of inflammatory cytokines and lymphoproliferation was assessed using monocyte-derived dendritic cells (moDCs) as antigen-presenting cells (APCs). The response was evaluated after exposing volunteers’ cells to each peptide. As a result, we learned that STI41 and STI46 peptides induced IL-8 and IL-12 in moDCs and lymphoproliferation and low levels of IL-10 in lymphocytes differentially in resistant volunteers, similar behavior to that observed in those individuals to L. panamensis lysate antigens. We conclude that, in silico analysis allowed for the identification of natural Leishmania epitopes in humans, and also STI41 and STI46 peptides could be epitopes that lead to a cellular immune response directed at parasite control.

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Section: In Silico Analysis For T Epitopesmentioning

confidence: 99%

Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

Flórez

Rodríguez

Cabrera³

et al. 2021

Front. Cell. Infect. Microbiol.

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Bajo polimorfismo en el sistema de antígenos de leucocitos humanos en población mestiza colombiana

Ávila-Portillo

Carmona

Franco³

et al. 2010

Univ. Med.

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Objetivo. Este trabajo tiene como objetivo describir la frecuencia de alelos y de haplotipos de antígenos HLA de clases I y II en población mestiza colombiana.Metodología. Se estudiaron 197 individuos colombianos no emparentados y 157 individuos emparentados que conformaban 53 familias, provenientes de diferentes regiones del país, remitidos para estudios de HLA de clases I y II por el método PCR-SSP a los laboratorios de inmunología del Hospital Militar Central de Bogotá y al Instituto de Referencia Andino.Resultados. El haplotipo HLA-A*24 B*35 DR*04 fue el más frecuente en la población estudiada, lo cual concuerda con otros estudios de mestizos colombianos.Conclusiones. El desequilibrio de Hardy-Weinberg hallado en la población analizada en el presente estudio, debe alertar sobre una eventual reducción en el repertorio de respuesta inmunitaria en los colombianos, lo cual podría ser el origen de una consecuente fragilidad de la población frente a nuevas infecciones que podrían convertirse en epidemias.

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Binding predictions and molecular docking as a computational approach to identify human T CD4 epitopes from Leishmania proteins

Martínez,

Larios,

Martínez

et al. 2024

Preprint

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Leishmaniasis is an important public health problem caused by a protozoan parasite and distributed in 98 countries worldwide. Leishmania can causes from skin ulcers to complex visceral involvement, and treatment options available for humans have high toxicity and prolonged application schemes, therefore low treatment adhesion. So far there are not licensed vaccines for humans so is necessary to develop a strategy that can improve treatment options or that can prevent the onset of the disease. To eliminate intracellular Leishmania amastigotes inside macrophage, a cellular immune response of CD4+ Th1 profile is essential, therefore the identification of sequences that binds strong to HLA class II pockets are good candidates to induce a protective immune response against Leishmania spp. The aim of this study was to identify T CD4+ epitopes from immunogenic Leishmania proteins. Methodology: First, three prediction tools were used as screening comparing the 15mer sequences along the complete protein sequence against 25 HLA-DR alleles employing NH, SMT, CPA, CPB, and CPC proteins. Second, molecular docking was run for the best candidates. Results: 6 peptides were identified as HLA-DR strong binders simultaneously from the three bioinformatic prediction tools: NH69-83, SMT133-148, CPA39-54, CPA301-316, CPB42-57, and CPC37-52. After alignment and molecular docking analysis, the most promising sequences were SMT113-148 and CPA39-54. Conclusion: This bioinformatic strategy allowed a sequential screening from 1 857 possible peptides to 2 promising candidates, raising the probability of these sequences being natural T CD4+ Leishmania spp. epitopes in humans, therefore good candidates to be evaluated in further studies.

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Polimorfismos del sistema HLA (loci A, B y DRB1*) en población colombiana

Cited by 7 publications

References 12 publications

Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

Leishmania spp Epitopes in Humans Naturally Resistant to the Disease: Working Toward a Synthetic Vaccine

Bajo polimorfismo en el sistema de antígenos de leucocitos humanos en población mestiza colombiana

Binding predictions and molecular docking as a computational approach to identify human T CD4 epitopes from Leishmania proteins

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