Structural Allele-Specific Patterns Adopted by Epitopes in the MHC-I Cleft and Reconstruction of MHC:peptide Complexes to Cross-Reactivity Assessment

The immune system is engaged in a constant antigenic surveillance through the Major Histocompatibility Complex (MHC) class I antigen presentation pathway. This is an efficient mechanism for detection of intracellular infections, especially viral ones. In this work we describe conformational patterns shared by epitopes presented by a given MHC allele and use these features to develop a docking approach that simulates the peptide loading into the MHC cleft. Our strategy, to construct in silico MHC:peptide complexes, was successfully tested by reproducing four different crystal structures of MHC-I molecules available at the Protein Data Bank (PDB). An in silico study of cross-reactivity potential was also performed between the wild-type complex HLA-A2-NS31073 and nine MHC:peptide complexes presenting alanine exchange peptides. This indicates that structural similarities among the complexes can give us important clues about cross reactivity. The approach used in this work allows the selection of epitopes with potential to induce cross-reactive immune responses, providing useful tools for studies in autoimmunity and to the development of more comprehensive vaccines

The impact of environmental effects on active galactic nuclei: A decline in the incidence of ionized outflows

This is an Open Access article, published by EDP Sciences, under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Active galactic nuclei (AGNs) have generally been considered to be less frequent in denser environments due to a lower number of galaxy-galaxy interactions and/or the removal of their gas-rich reservoirs by the dense intergalactic medium. However, recent observational and theoretical works suggest that the effect of ram-pressure stripping acting on galaxies in dense environments might reduce the angular momentum of their gas, causing it to infall towards the super massive black hole at their centre, activating the AGN phase. In this work we explore the connection between environment and nuclear activity by evaluating the variation in the incidence of ionized outflows, a common phenomenon associated with nuclear activity, in AGNs across different environments. We select a sample of approximately 3300 optical AGNs from the Sloan Digital Sky Survey Data Release 13, which we match with a group catalogue to identify galaxies in isolation or residing in groups. We further probe their environments through the projected distance to the central galaxy of the group or cluster and the projected surface density to the fifth neighbour (δ5). The presence of ionized outflows is determined through the modelling of the [O III] λ5007 emission line. We find that at lower masses (< 1010.3 M⊙), the fraction of ionized outflows is significantly lower in satellite AGNs (∼7%) than in isolated (∼22%) AGNs, probably due to their different AGN luminosity, L[O III], in this stellar mass range. The fraction of outflows decreases at distances closer to the central galaxy of the group or cluster for all satellite AGNs; however, only the lower-mass ones (109 − 1010.3 M⊙) display a significant decline with δ5. Although this study does not include AGNs in the densest regions of galaxy clusters, our findings suggest that AGNs in dense environments accrete less gas than those in the field, potentially due to the removal of the gas reservoirs via stripping or starvation, leading to a negative connection between environment and AGN activity. Based on our results, we propose that the observed change in the incidence of outflows when moving towards denser regions of groups and clusters could contribute to the higher gas metallicities of cluster galaxies compared to field galaxies, especially at lower masses. © The Authors 2023.B.R.D.P., S.A. and M.P. acknowledge support from the Spanish Ministerio de Economía y Competitividad through the grants PID2019-106280GB-I00 and PID2021-127718NB-I00. A.L.C.S. acknowledges funding from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Rio Grande do Sul Research Foundation (FAPERGS) through grant CNPq-314301/2021-6 and FAPERGS/CAPES 19/2551-0000696-9. I.L. acknowledges support from the Spanish Ministry of Science and Innovation (MCIN) by means of the Recovery and Resilience Facility, and the Agencia Estatal de Investigación (AEI) under the projects BDC20221289 and PID2019-105423GA-I00. M.P. acknowledges support from the Programa Atracción de Talento de la Comunidad de Madrid via grant 2018-T2/TIC-11715. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS-IV acknowledges support and resources from the centre for High-Performance Computing at the University of Utah. The SDSS web site is https://www.sdss.org/. This research made use of Astropy, a community-developed core Python package for Astronomy (Astropy Collaboration 2018). This research has made use of the NASA/IPAC Extragalactic Database (NED) which is operated by the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.With funding from the Spanish government through the "Severo Ochoa Centre of Excellence" accreditation (CEX2021-001131-S).Peer reviewe

New evidence for balancing selection at the HLA-G locus in South Amerindians

HLA-G is a non-classical HLA (Human Leukocyte Antigen) molecule characterized by limited tissue distribution under normal physiological conditions and low variability at both DNA and protein levels. Several studies suggest that HLA-G could play a role, as an immunoregulatory molecule, in situations as diverse as transplantation, cancer, viral infections and inflammatory diseases. A total of 237 individuals from 21 South American tribes speaking nine different linguistic families were studied in relation to the 14 bp insertion/deletion polymorphism at the HLA-G gene. A consistent (seven in nine) excess of heterozygosity in samples classified by language was obtained. Our data supply evidences for balancing selection acting at the HLA-G 14 bp INDEL region. Enhanced fetal survival in a pathogen-rich environment may account for these findings