Identification, cloning, and sequencing of different cytokine genes in four species of owl monkey

Hernández, E. C.; Suárez, Carlos F.; Méndez, Jairo A.; Echeverry, Sandra J.; Murillo, Luis A.; Patarroyo, Manuel E.

doi:10.1007/s00251-002-0512-2

Cited by 20 publications

(12 citation statements)

References 22 publications

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“…It has also been shown the same peptide can be presented within the context of different alleles from the same HLA-DRβ1*molecules, as happens with the Myelin Basic Protein peptide (MBP [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102]. This peptide has been seen to bind to HLA-DRβ5* 0101 and DRβ1*1501 molecules in 2 totally different functional registers [132].…”

Section: General Considerationsmentioning

confidence: 96%

“…Molecular biology studies have shown that Aotus monkeys possess a very similar immune system to that of humans where molecules such as immunoglobulin heavy and light chains [83], cytokines [84], T-lymphocyte γδ [85], α [86] and β [87] T-cell receptors, MHC class-I molecules [88], CD 1 [89] and HLA-DP- [90], DQ- [91] and DR- [5,92] like Class-II molecules are highly similar (almost identical) to those of humans. This high degree of homology between this New World primate's immune system molecules and those of humans reaffirms the importance of Aotus monkeys as a suitable experimental model for studying and developing vaccines for human use against infectious diseases such as tuberculosis, leprosy, leishmaniasis and malaria.…”

Section: Aotus Monkey Immunogeneticsmentioning

confidence: 99%

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Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Patarroyo

Cifuentes

Salazar

et al. 2005

CMC

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An anti-malarial vaccine is urgently needed, especially against P. falciparum which causes 2 to 3 million deaths each year, mostly in Sub-Saharan African children. This vaccine should contain molecules from the parasite's different developmental stages due to the parasite's remarkable complexity and genetic variability. The first approach using synthetic peptides from different parasite stage molecules (the SPf66 malaria vaccine) conferred limited protective efficacy in Aotus monkeys and in large field-trials carried out in different parts of the world SPf66 contains red blood cell (RBC) binding merozoite peptides for which immune responses against them are genetically controlled by HLA-DR region. Therefore, a systematic search of conserved high activity binding peptides (HABP) was undertaken aimed at using them as immunogens. However, these peptides were poorly immunogenic and had poor protection-inducing capacity against experimental challenge with a P. falciparum strain highly infective for Aotus monkeys an experimental model with an immune system quite similar to humans. Modifications were thus made to key residues to render them immunogenic and protection-inducing. These native and modified HABPs' three-dimensional structure was determined by (1)H-NMR studies and their ability in forming stable Major Histocompatibility Class II - peptide (MHCII-peptide) complexes was correlated with their ability to bind in vitro to purified HLA-DR beta1* molecules. Our experimental data suggests a correlation between modified HABPs' three-dimensional structure, HLA-DR beta1* binding preferences and their protection-inducing capacity in monkeys. Furthermore, the data presented here indicates that a synthetic peptide vaccine's three-dimensional structural features dictate both HLA-DR beta1* allele binding preference (imposing genetic restriction on the immune response) and on these vaccines' protection-inducing value. Basic knowledge of a parasite's functionally active peptides, their 3D structure and their interaction for forming the MHC II- peptide-TCR complex will thus contribute towards designing fully effective multi-component, multi-stage subunit-based malarial vaccines.

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Section: General Considerationsmentioning

confidence: 96%

Section: Aotus Monkey Immunogeneticsmentioning

confidence: 99%

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Patarroyo

Cifuentes

Salazar

et al. 2005

CMC

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“…This data and previous work on the A . nancymaae TCR repertoire (28, 32, 33), major histocompatibility complex diversity (27, 29, 31), kappa light‐chain V, J, and C (30), and cytokine genes (26) support the view of using Aotus monkeys being used as an experimental animal model for testing epitope‐focused peptide vaccines against Plasmodium falciparum and other infectious diseases. However, Aotus CD45 functional studies are necessary for defining the role of CD45 during lymphocyte activation and signal transduction, and the contribution (if any) of the differences found here towards understanding its function and regulation.…”

Section: Discussionmentioning

confidence: 91%

“…Several proteins having functional importance for the Aotus immune system have been recently described in our Institution (26–33) to confirm this experimental model's suitability for evaluating potential vaccine candidates (34). This report presents a comparison of the complete CD45 amino acid sequences from three Aotus species ( Aotus nancymaae , Aotus nigriceps , and A .…”

mentioning

confidence: 76%

Comparative analysis of CD45 proteins in primate context: owl monkeys vs humans

Patarroyo

2004

Tissue Antigens

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Transmembrane protein tyrosine phosphatase (PTPase) CD45 has been implicated in activating, differentiating and the development of different immune system cells. It regulates T-or B-cell activation during receptor-specific recognition by dephosphorylating tyrosine residues in protein kinase substrates. Aotus nancymaae, Aotus nigriceps, and Aotus vociferans CD45 nucleotide and deduced amino acid sequences are presented here, where we found 90-92% identity with the human counterpart in the nucleotide sequence and 83-86% in the amino acid sequence. Aotus CD45 alternative splicing isoforms include the same exons used in human CD45, producing several identical molecular weight nucleotide fragments. Most of the non-synonymous substitutions were found in the extracellular domain. The more conserved CD45 cytoplasmic portion has two intracellular phosphatase domains (D1 and D2) separated by a short spacer and some residues and motifs involved in signaling or molecular docking, intra- and intermolecular interactions and CD45 activity and activity regulation. All invariant residues and structural/functional motifs found in PTPases were totally conserved, suggesting that Aotus CD45 is a functional enzyme. Phylogenetic analysis has shown that the Aotus CD45 molecules are more related to the human homologs than to other reported vertebrate sequences and that the ancestral group of Aotus clade is A. vociferans. When Aotus species were compared, A. nigriceps and A. vociferans were the two most distant species, while A. nancymaae and A. nigriceps appeared to be a sister group. This could be relevant in deciding which Aotus species is to be used for studying particular immunological processes during lymphocyte activation or development.

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“…Aunque la interacción de péptidos antigénicos con moléculas extremadamente polimórficas como las de clase II representa uno de los mayores obstáculos para la identificación de epítopes universales y diseño de vacunas sintéticas, muchos trabajos recientes por ejemplo: (i) estudios de cristalografía de rayos X han definido las características del bolsillo de unión, mostrando preferencias entre alelos para su interacción con cadenas laterales de los aminoácidos en los péptidos; (ii) la generación de datos experimentales, de ensayos de unión in vitro entre péptidos y moléculas MHC purificadas (23); (iii) la caracterización a través del mapeo de proteínas y péptidos de respuestas de cé-lulas efectoras especificas contra péptidos; (iv) la identificación de residuos críticos para la interacción del péptido con el receptor de las células T para el antígeno (TCR) y (v) el reciente aporte de la informática al campo, que ha hecho posible la identificación de "motivos universales" y matrices virtuales HLA clase II, lo anterior ha permitido mejor comprensión de las interacciones entre péptidos y estas moléculas, y quizás conlleve en un futuro, a esclarecer adecuadamente las característi-cas de posibles epitopes universales. Desde los puntos de vista estructural y funcional, la caracterización de péptidos exógenos con capacidad de unión a varios alelos (promiscuidad de unión) que se hallan presentes en distintas poblaciones (43-47) y su posible asociación con la resistencia o susceptibilidad a enfermedades infecciosas, son una herramienta muy poderosa para diseñar vacunas sinté-ticas en las que se combinan fragmentos de longitud variable (48)(49)(50)(51). Mediante esta estrategia se busca asegurar una protección duradera y efectiva frente a microorganismos patógenos en cualquier población.…”

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Complejo mayor de histocompatibilidad y desarrollo de vacunas

Torres

Gama

2004

nova

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IntroducciónDentro de las funciones más importantes de los linfocitos T están la defensa frente a microorganismos intracelulares y la activación de otras células, como macrófagos y linfocitos B. Una característica esencial para estas funciones es la especificidad limitada de los linfocitos T por los antígenos mostrados por las Complejo mayor de histocompatibilidad y desarrollo de vacunas ResumenSin duda, las vacunas se constituyen en una alternativa viable y efectiva para el control de las enfermedades infectocontagiosas, sin embargo, una estrategia exitosa para el diseño de vacunas debe tener en consideración muchos de los aspectos de la respuesta inmune en una población heterogénea y en su forma de reconocer y presentar los antígenos de los patógenos. Por lo tanto, no solamente el entendimiento preciso de los mecanismos inmunes involucrados en la resistencia a infecciones sino la identificación de las moléculas del patógeno que son el blanco de respuesta protectora, serán motivo central de la investigación en vacunas en el futuro inmediato. El presente artículo de revisión profundiza en el descubrimiento, ubicación, expresión, estructura, herencia, polimorfismo e importancia del complejo mayor de histocompatibilidad; además, presenta los avances en elo uso de primates como modelo para el desarrollo de vacunas.Palabras claves: vacuna, MHC, histocompatibilidad, primates, herencia, desarrollo. Abstract Mayor complex histocompatibility and vaccines development.Without doubt, the vaccines are the most viable and effective alternative for the control of the contagious infected diseases, however, a successful strategy for the vaccines design must have in consideration many of the aspects of exempt response in a heterogeneous population and in your form of recognizing and presenting the antigens of the patogens. Therefore, not only the accurate understanding of the exempt mechanisms involved in the resistance to infections but the identification of the molecules of the patogen that they are protective response target, they will be central motive of the investigation in vaccines in the immediate future.The present review article deepens in the discovery, location, expression, structure, inheritance, polymorphism and importance of major complex hispocompatibility, and presents the advances in the use of primates as model for the vaccines development.

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Identification, cloning, and sequencing of different cytokine genes in four species of owl monkey

Cited by 20 publications

References 22 publications

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Comparative analysis of CD45 proteins in primate context: owl monkeys vs humans

Complejo mayor de histocompatibilidad y desarrollo de vacunas

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Identification, cloning, and sequencing of different cytokine genes in four species of owl monkey

Cited by 20 publications

References 22 publications

Based on HLA-DR&#946;1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Based on HLA-DR&#946;1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Comparative analysis of CD45 proteins in primate context: owl monkeys vs humans

Complejo mayor de histocompatibilidad y desarrollo de vacunas

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Product

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Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides

Based on HLA-DRβ1* Allele Binding Specificities, Striking Differences in Distance and TCR Contacting Residue Orientation can be Observed in Modified Protection-Inducing Malarial Synthetic Peptides