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The Pathway of Antigen Processing and Presentation
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The Pathway of Antigen Processing and Presentation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 11889

Special Issue Editor

Dr. Efstratios Stratikos

E-Mail Website
Guest Editor
Department of Chemistry, National and Kapodistrian University of Athens, 15784 Zografou, Greece
Interests: aminopeptidases; enzymes; antigen presentation; adaptive immunity; cancer; inflammation; inhibitors; drug-design
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The human adaptive immune system can sense infected or aberrant cells by detecting small peptides on the cell surface that belong to a pathogen or are generated due to cancerous transformation. These peptides, called antigenic peptides, are generated inside the cell by the specialized pathway of antigen processing and presentation. This pathway continuously samples the protein content of the cell and presents peptides bound onto major histocompatibility complex molecules on the cell surface. This Special Issue will focus on all molecular aspects of this important pathway, their role in health and disease, and their roles in regulating immune responses and efforts to pharmacologically modulate them for therapeutic purposes.

Dr. Efstratios Stratikos
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • major histocompatibility complex (MHC)
  • antigens
  • antigenic peptides
  • antigen processing
  • proteasome
  • tapasin
  • TAP
  • peptide-loading complex
  • adaptive immunity
  • autoimmunity
  • cancer immunotherapy
  • immunopeptidome
  • aminopeptidases
  • T lymphocytes
  • natural killer cells
  • human leukocyte antigens (HLAs)
  • T-cell receptor

Published Papers (4 papers)

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Research

16 pages, 2457 KiB  
Article
IgE and IgG4 Epitopes of Dermatophagoides and Blomia Allergens before and after Sublingual Immunotherapy
by Daniele Danella Figo, Priscilla Rios Cordeiro Macedo, Gabriele Gadermaier, Cesar Remuzgo, Fábio Fernandes Morato Castro, Jorge Kalil, Clovis Eduardo Santos Galvão and Keity Souza Santos
Int. J. Mol. Sci. 2023, 24(4), 4173; https://doi.org/10.3390/ijms24044173 - 20 Feb 2023
Cited by 3 | Viewed by 2221
Abstract
Sublingual immunotherapy (SLIT) is used worldwide to treat house dust mites (HDM) allergy. Epitope specific immunotherapy with peptide vaccines is used far less, but it is of great interest in the treatment of allergic reactions, as it precludes the drawbacks of allergen extracts. [...] Read more.
Sublingual immunotherapy (SLIT) is used worldwide to treat house dust mites (HDM) allergy. Epitope specific immunotherapy with peptide vaccines is used far less, but it is of great interest in the treatment of allergic reactions, as it precludes the drawbacks of allergen extracts. The ideal peptide candidates would bind to IgG, blocking IgE-binding. To better elucidate IgE and IgG4 epitope profiles during SLIT, sequences of main allergens, Der p 1, 2, 5, 7, 10, 23 and Blo t 5, 6, 12, 13, were included in a 15-mer peptide microarray and tested against pooled sera from 10 patients pre- and post-1-year SLIT. All allergens were recognized to some extent by at least one antibody isotype and peptide diversity was higher post-1-year SLIT for both antibodies. IgE recognition diversity varied among allergens and timepoints without a clear tendency. Der p 10, a minor allergen in temperate regions, was the molecule with more IgE-peptides and might be a major allergen in populations highly exposed to helminths and cockroaches, such as Brazil. SLIT-induced IgG4 epitopes were directed against several, but not all, IgE-binding regions. We selected a set of peptides that recognized only IgG4 or were able to induce increased ratios of IgG4:IgE after one year of treatment and might be potential targets for vaccines. Full article
(This article belongs to the Special Issue The Pathway of Antigen Processing and Presentation)
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11 pages, 1271 KiB  
Article
The rs1883832 Polymorphism (CD40-1C>T) Affects the Intensity of IgA Responses after BNT162b2 Vaccination
by Matthaios Speletas, Evangelos Bakaros, Athanasia-Marina Peristeri, Ioanna Voulgaridi, Styliani Sarrou, Vassiliki Paliatsa, Asimina Nasika, Maria Tseroni, Lemonia Anagnostopoulos, Kalliopi Theodoridou, Fani Kalala, Aikaterini Theodoridou, Barbara A. Mouchtouri, Sotirios Tsiodras, Hermann Eibel and Christos Hadjichristodoulou
Int. J. Mol. Sci. 2022, 23(22), 14056; https://doi.org/10.3390/ijms232214056 - 14 Nov 2022
Cited by 6 | Viewed by 1405
Abstract
The effectiveness of coronavirus disease 2019 (COVID-19) vaccination strategies is affected by several factors, including the genetic background of the host. In our study, we evaluated the contribution of the functional polymorphism rs1883832 affecting the Kozak sequence of the TNFSF5 gene (c.-1C>T), encoding [...] Read more.
The effectiveness of coronavirus disease 2019 (COVID-19) vaccination strategies is affected by several factors, including the genetic background of the host. In our study, we evaluated the contribution of the functional polymorphism rs1883832 affecting the Kozak sequence of the TNFSF5 gene (c.-1C>T), encoding CD40, to humoral immune responses after vaccination with the spike protein of SARS-CoV-2. The rs1883832 polymorphism was analyzed by PCR-RFLP in 476 individuals (male/female: 216/260, median age: 55.0 years, range: 20–105) of whom 342 received the BNT162b2 mRNA vaccine and 134 received the adenovirus-based vector vaccines (67 on ChAdOx1-nCoV-19 vaccine, 67 on Ad.26.COV2.S vaccine). The IgG and IgA responses were evaluated with chemiluminescent microparticle and ELISA assays on days 21, 42, and 90 after the first dose. The T allele of the rs1883832 polymorphism (allele frequency: 32.8%) was significantly associated with lower IgA levels and represented, as revealed by multivariable analysis, an independent risk factor for reduced anti-spike protein IgA levels on days 42 and 90 following BNT162b2 mRNA vaccination. Similar to serum anti-spike IgA levels, a trend of lower anti-spike IgA concentrations in saliva was found in individuals with the T allele of rs1883832. Finally, the intensity of IgA and IgG responses on day 42 significantly affected the prevalence of COVID-19 after vaccination. The rs1883832 polymorphism may be used as a molecular predictor of the intensity of anti-spike IgA responses after BNT162b2 mRNA vaccination. Full article
(This article belongs to the Special Issue The Pathway of Antigen Processing and Presentation)
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15 pages, 3177 KiB  
Article
ERAP/HLA-C and KIR Genetic Profile in Couples with Recurrent Implantation Failure
by Karolina Piekarska, Paweł Radwan, Agnieszka Tarnowska, Michał Radwan, Jacek R. Wilczyński, Andrzej Malinowski and Izabela Nowak
Int. J. Mol. Sci. 2022, 23(20), 12518; https://doi.org/10.3390/ijms232012518 - 19 Oct 2022
Cited by 2 | Viewed by 4917
Abstract
Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human [...] Read more.
Proper embryo implantation depends on the tolerance of the maternal immune system to the fetus and its foreign paternal antigens. During implantation and early pregnancy, the dominant leukocytes in the uterus are uterine NK cells, expressing killer immunoglobulin-like receptors (KIR). KIRs recognize human leukocyte antigens (HLA-C) on the human trophoblast inherited from the father and mother. The antigenic peptides presented by the HLA are formed via their cleavage by endoplasmic reticulum aminopeptidases ERAP1 and ERAP2. The aim of this study was to assess the association of combined KIR genes and their HLA-C ligands, as well as ERAP1 and ERAP2 polymorphisms with recurrent implantation failure after in vitro fertilization (RIF). We tested 491 couples who underwent in vitro fertilization (IVF) and 322 fertile couples. Genotype CC rs27044 ERAP1 in female with a male’s HLA-C1C1 or HLA-C1C2 protected from RIF (p/pcorr. = 0.005/0.044, OR = 0.343; p/pcorr. = 0.003/0.027, OR = 0.442, respectively). Genotype TT rs30187 ERAP1 in female with a male’s HLA-C1C2 genotype increased the risk of RIF. Summarizing, in the combination of female ERAP1 and an HLA-C partner, the rs30187 C>T and rs27044 C>G polymorphisms play an important role in implantation failure. Full article
(This article belongs to the Special Issue The Pathway of Antigen Processing and Presentation)
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12 pages, 1663 KiB  
Article
ERAP2 Inhibition Induces Cell-Surface Presentation by MOLT-4 Leukemia Cancer Cells of Many Novel and Potentially Antigenic Peptides
by Ioannis Temponeras, George Stamatakis, Martina Samiotaki, Dimitris Georgiadis, Harris Pratsinis, George Panayotou and Efstratios Stratikos
Int. J. Mol. Sci. 2022, 23(3), 1913; https://doi.org/10.3390/ijms23031913 - 8 Feb 2022
Cited by 5 | Viewed by 2470
Abstract
Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy of immune-checkpoint inhibitor cancer immunotherapy, suggesting that pharmacological inhibition of ERAP2 could have important therapeutic implications. To explore the effects of ERAP2 inhibition on the immunopeptidome of cancer cells, [...] Read more.
Recent studies have linked the activity of ER aminopeptidase 2 (ERAP2) to increased efficacy of immune-checkpoint inhibitor cancer immunotherapy, suggesting that pharmacological inhibition of ERAP2 could have important therapeutic implications. To explore the effects of ERAP2 inhibition on the immunopeptidome of cancer cells, we treated MOLT-4 T lymphoblast leukemia cells with a recently developed selective ERAP2 inhibitor, isolated Major Histocompatibility class I molecules (MHCI), and sequenced bound peptides by liquid chromatography tandem mass spectrometry. Inhibitor treatment induced significant shifts on the immunopeptidome so that more than 20% of detected peptides were either novel or significantly upregulated. Most of the inhibitor-induced peptides were 9mers and had sequence motifs and predicted affinity consistent with being optimal ligands for at least one of the MHCI alleles carried by MOLT-4 cells. Such inhibitor-induced peptides could serve as triggers for novel cytotoxic responses against cancer cells and synergize with the therapeutic effect of immune-checkpoint inhibitors. Full article
(This article belongs to the Special Issue The Pathway of Antigen Processing and Presentation)
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