Biology subjects

Pacheco-Olvera, D. L.

Publications and source records attributed to Pacheco-Olvera, D. L..

2 recordsLinked to original sources

bioRxiv2022

Subfunctionalization and constrained size of the immunoglobulin loci in Ambystoma mexicanum

BackgroundThe axolotl, Ambystoma mexicanum is a unique biological model for complete tissue regeneration. Is a neotenic endangered species and is highly susceptible to environmental stress, including infectious disease. In contrast to other amphibians, the axolotl is particularly vulnerable to certain viral infections. Like other salamanders, the axolotl genome is one of the largest (32 Gb) and the impact of genome size on Ig loci architecture is unknown. To better understand the immune response in axolotl, we aimed to characterize the immunoglobulin loci of A. mexicanum and compare it with other model tetrapods. MethodsThe most recently published genome sequence of A. mexicanum (V6) was used for alignment-based annotation and manual curation using previously described axolotl Ig sequences or reference sequences from other tetrapods. Gene models were further curated using A. mexicanum spleen RNA-seq data. Human reference genomes, Xenopus tropicalis, and Danio rerio (zebrafish) were used for comparison. ResultsCanonical A. mexicanum Heavy chain (IGH), lambda (IGL), sigma (IGS) and Surrogate light chain (SLC) loci were identified. No kappa locus was found. More than half of the IGHV genes and the IGHF gene are pseudogenes, there are no clan I IGHV genes and CDRH3 diversity is restricted. Although the IGH locus size is proportional to genome size, we found local size restriction in the IGHM gene and in the V gene intergenic distances. In addition, there were V genes with abnormally large V-intron sizes, which correlated with loss of gene functionality. ConclusionThe A. mexicanum immunoglobulin loci share the same general genome architecture as most studied tetrapods. Consistent with its large genome, Ig loci are larger; however, local size restrictions indicate evolutionary constraints likely to be imposed by high transcriptional demand of certain Ig genes, as well as the V(D)J recombination over very long genomic distance ranges. The A. mexicanum has undergone an extensive process of pseudogenization which partially explains a reduced potential repertoire diversity that may contribute to its impaired antibody response.

immunology↗

bioRxiv2020

Bioinformatic analysis of shared B and T cell epitopes amongst relevant coronaviruses to human health: Is there cross-protection?

Within the last 30 years 3 coronaviruses, SARS-CoV, MERS-CoV and SARS-CoV-2, have evolved and adapted to cause disease and spread amongst the human population. From the three, SARS-CoV-2 has spread world-wide and to July 2020 it has been responsible for more than 11 million confirmed cases and over half a million deaths. In the absence of an effective treatment or vaccine, social distancing has been the most effective measure to control the pandemic. However it has become evident that as the virus spreads the only tool that will allow us to fully control it is an effective vaccine. There are currently more than 150 vaccine candidates in different stages of development using a variety of viral antigens, with the S protein being the most targeted antigen. Although some new experimental evidence suggests cross-reacting responses between coronaviruses are present in the population, it remains unknown whether potential shared antigens between different coronaviruses could provide cross-protection. Given that coronaviruses are emerging pathogens and continue to represent a threat to global health, the development of a SARS-Cov-2 vaccine that could provide universal protection against other coronaviruses should be pushed forward. Here we present a thorough review of reported B and T cell epitopes shared between SARS-CoV-2 and other relevant coronaviruses, in addition we used web-based tools to predict novel B and T cell epitopes that have not been reported before. Analysis of experimental evidence that is constantly emerging complemented with the findings of this study allow us support the hypothesis that cross-reactive responses, particularly those coming from T cells, might play a key role in controlling infection by SARS-CoV-2. We hope that with the evidence presented in this manuscript we provide arguments to encourage the study of cross-reactive responses in order to elucidate their role in immunity to SARS-CoV-2. Finally we expect our findings will aid targeted analysis of antigen-specific immune responses and guide future vaccine design aiming to develop a cross reactive effective vaccine against respiratory diseases caused by coronaviruses.

immunology↗