DOCSLIB.ORG

Phylogenetic Analysis of the Human Antibody Repertoire Reveals Quantitative Signatures of Immune Senescence and Aging

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Phylogenetic Analysis of the Human Antibody Repertoire Reveals Quantitative Signatures of Immune Senescence and Aging Phylogenetic analysis of the human antibody repertoire reveals quantitative signatures of immune senescence and aging Charles F. A. de Bourcya, Cesar J. Lopez Angelb, Christopher Vollmersc,1, Cornelia L. Dekkerd, Mark M. Davisb,e,f, and Stephen R. Quakea,c,g,2 aDepartment of Applied Physics, Stanford University, Stanford, CA 94305; bDepartment of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305; cDepartment of Bioengineering, Stanford University, Stanford, CA 94305; dDepartment of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305; eInstitute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford, CA 94305; fHoward Hughes Medical Institute, Chevy Chase, MD 20815; and gChan Zuckerberg Biohub, San Francisco, CA 94158 Contributed by Stephen R. Quake, December 15, 2016 (sent for review November 4, 2016; reviewed by Nir Hacohen and Rob Knight) The elderly have reduced humoral immunity, as manifested by hypervariable complementarity-determining region 3 (CDR3) in increased susceptibility to infections and impaired vaccine re- Ig heavy-chain (IGH) transcripts (8, 9). sponses. To investigate the effects of aging on B-cell receptor Elderly individuals’ B-cell repertoires have been reported to (BCR) repertoire evolution during an immunological challenge, we exhibit restricted clonal diversity, oligoclonal character, increased used a phylogenetic distance metric to analyze Ig heavy-chain baseline mutation levels, and persistent clonal expansions in pre- transcript sequences in both young and elderly individuals before vious studies of IGH sequence diversity (8, 10). However, previous and after influenza vaccination. We determined that BCR reper- work was limited by small numbers of elderly individuals analyzed toires become increasingly specialized over a span of decades, but (8), did not analyze in detail the composition of the oligoclonal less plastic. In 50% of the elderly individuals, a large space in the lineages (8), or did not study the effect of applying an immune repertoire was occupied by a small number of recall lineages that did + stimulus such as a vaccine (10). Furthermore, previous B-cell not decline during vaccine response and contained hypermutated IgD repertoire studies have focused only on isolated aspects of B-cell B cells. Relative to their younger counterparts, older subjects demon- INFLAMMATION mutation counts, V/D/J-gene use levels, lineage sizes, and con- IMMUNOLOGY AND strated a contracted naive repertoire and diminished intralineage di- vergent CDR3 sequences (8, 10–13) without analyzing the char- versification, signifying a reduced substrate for mounting novel acter of mutations and without using the full phylogenetic responses and decreased fine-tuning of BCR specificities by somatic information inherent in the IGH repertoire to quantify dissimi- hypermutation. Furthermore, a larger proportion of the repertoire larities between immune systems. exhibited premature stop codons in some elderly subjects, indicating Here, we identify signatures of immune aging by carrying out a that aging may negatively affect the ability of B cells to discriminate phylogenetic analysis of IGH transcripts in the peripheral blood between functional and nonfunctional receptors. Finally, we observed of healthy young and elderly volunteers before and after in- a decreased incidence of radical mutations compared with conservative fluenza vaccination. First, we study the increasing specialization mutations in elderly subjects’ vaccine responses, which suggests that accumulating original antigenic sin may be limiting the accessible space for paratope evolution. Our findings shed light on the complex inter- Significance play of environmental and gerontological factors affecting immune senescence, and provide direct molecular characterization of the effects The world’s population is growing older, and senescence of the of senescence on the immune repertoire. immune system is a fundamental factor underlying morbidity and mortality. We report a direct molecular characterization of the ef- aging | antibody repertoire | influenza vaccine | CMV | UniFrac fects of aging on the adaptive immune system by high-throughput sequencing of antibody transcripts in the peripheral blood of hu- mans. Using a phylogenetic approach to quantify dissimilarity, we he deterioration of immune function with age, a process re- compared the immunoglobulin repertoires of young and elderly ferred to as immunosenescence, is well recognized. Notable T individuals at baseline and during a well-defined immunogenic changes contributing to immunosenescence include, among others, perturbation in the form of influenza vaccination; we also studied decreased proliferation of lymphocytes, reduced T-cell re- the long-term effects of chronic infection. Our work reveals pre- ceptor repertoire, and defects in antibody production (1, 2). viously unappreciated signatures of immune senescence that may This phenomenon contributes to an age-related increase in find diagnostic use and guide approaches for improving elderly susceptibility to viral and bacterial infections and decreased patients’ antibody responses. response to vaccination (3–5). Indeed, individuals over the age of 65 y are less than half as protected by standard influenza Author contributions: C.F.A.d.B., C.J.L.A., C.L.D., M.M.D., and S.R.Q. designed research; C.F.A.d.B., vaccines as younger individuals (6), and pneumonia and in- C.J.L.A., and C.V. performed research; C.F.A.d.B. and S.R.Q. analyzed data; and C.F.A.d.B., fluenza represent the fourth most common cause of death C.J.L.A., and S.R.Q. wrote the paper. among aging individuals (4). Reviewers: N.H., Massachusetts General Hospital; and R.K., University of California, Antibody-mediated immunity is the result of an evolutionary San Diego. arms race between the pathogens to which an individual is ex- Conflict of interest statement: Dr. Quake and Dr. Knight were coauthors on Biteen JS, et al. (2015) Tools for the microbiome: Nano and beyond. ACS Nano 10(1):6–37. This was a posed and antibody-producing B cells. A tremendous diversity of perspective and did not involve any active research collaboration. potential antibody affinities is generated by the mechanisms of Data deposition: The sequence reported in this paper has been deposited in the National V(D)J recombination, random junctional insertions/deletions, and Center for Biotechnology Information BioProject (accession no. PRJNA356133). somatic hypermutation (7). Preferential proliferation of activated 1Present address: Department of Biomolecular Engineering, University of California, B cells upon encounter with a cognate antigen then exerts a se- Santa Cruz, CA 95064. lective pressure for B-cell receptors (BCRs) with a high binding 2To whom correspondence should be addressed. Email: [email protected]. affinity to the antigen (7). The clonal history of B cells circulating This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10. in the blood can be traced using next-generation sequencing of the 1073/pnas.1617959114/-/DCSupplemental. www.pnas.org/cgi/doi/10.1073/pnas.1617959114 PNAS Early Edition | 1of6 Downloaded by guest on September 28, 2021 of the antibody repertoire by developing a phylogenetic distance natural to apply UniFrac to antibody repertoire sequence data. metric for the repertoire based on unique fraction (UniFrac) The original method based on a single gene (the 16S rRNA (14). Next, we analyze the prevalence of B-cell oligoclonality and gene) can be extended (20) to account for the use of multiple the composition of the relevant lineages in the elderly. Finally, genes (here, the various VDJ rearrangements). we examine the effect of age on vaccine response and its un- In our implementation of UniFrac, each group of sequences derlying factors, including the diversity of the substrate for novel having the same V-gene, J-gene, and CDR3 length is combined into responses, the somatic hypermutation process, and the clonal a phylogenetic tree rooted at a pseudo-germline sequence con- selection process. structed by masking any allelic or junctional differences between Our study comprised 10 healthy young subjects and 10 healthy participants. Because all groups originate from rearrangement of elderly subjects, with blood sampled at baseline, day 7, and day 28 the full heavy-chain locus, we consider all of the pseudo-germline relative to vaccination with the 2011 seasonal trivalent inactivated sequences to be at the same level, the root level, in the overall influenza vaccine (Fig. 1A and Table S1). Because immunose- phylogeny of repertoires. We then compute a weighted UniFrac nescence has been reported to be more pronounced in men (15), distance on the overall phylogenetic tree encompassing all groups as only male subjects were chosen. Because chronic infection with described in SI Materials and Methods. Applying UniFrac to a the widespread cytomegalovirus (CMV) is known to be a con- separate cohort of young individuals sampled at eight time points founding factor in the study of immune aging (10), we stratified over the course of 2 wk indicated that changes in a participant’s the analysis by CMV serostatus assessed by IgG ELISA. repertoire composition over a span of 2 wk were resolvable but substantially smaller than differences between individuals (Fig. S1). Results Applying UniFrac to our main cohort indicated that aging in- Divergent Evolution of Immune Systems Quantified
Load more

Recommended publications
  • Efficiency of the Immunome Protein Interaction Network Increases During Evolution Csaba Ortutay*1 and Mauno Vihinen1,2
    Immunome Research BioMed Central Research Open Access Efficiency of the immunome protein interaction network increases during evolution Csaba Ortutay*1 and Mauno Vihinen1,2 Address: 1Institute of Medical Technology, FI-33014 University of Tampere, Finland and 2Tampere University Hospital, FI-33520 Tampere, Finland Email: Csaba Ortutay* - [email protected]; Mauno Vihinen - [email protected] * Corresponding author Published: 22 April 2008 Received: 23 January 2008 Accepted: 22 April 2008 Immunome Research 2008, 4:4 doi:10.1186/1745-7580-4-4 This article is available from: http://www.immunome-research.com/content/4/1/4 © 2008 Ortutay and Vihinen; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Details of the mechanisms and selection pressures that shape the emergence and development of complex biological systems, such as the human immune system, are poorly understood. A recent definition of a reference set of proteins essential for the human immunome, combined with information about protein interaction networks for these proteins, facilitates evolutionary study of this biological machinery. Results: Here, we present a detailed study of the development of the immunome protein interaction network during eight evolutionary steps from Bilateria ancestors to human. New nodes show preferential attachment to high degree proteins. The efficiency of the immunome protein interaction network increases during the evolutionary steps, whereas the vulnerability of the network decreases. Conclusion: Our results shed light on selective forces acting on the emergence of biological networks.
    [Show full text]
  • Immunome-Derived Epitope-Driven Vaccines (ID-EDV)
    Available online at www.sciencedirect.com Procedia in Vaccinology 1 (2009) 15–22 2nd Vaccine Global Congress, Boston 2008 Immunome-derived Epitope-driven Vaccines (ID-EDV) Protect against Viral or Bacterial Challenge in Humanized Mice Lenny Moisea,b, Matt Arditoa, Joe Desrosiersa, Jill Schriewerc, Mark Bullerd, Sharon E. Freyd, Stephen H. Gregoryb,e, Steven F. Mossb,d, Jinhee Leee, Hardy Kornfeld e, Bill Martina, Anne S. De Groota,b,c,* * aEpiVax, 146 Clifford Street, Providence, RI 02903, USA bAlpert Medical School, Brown University, Providence, RI 02903, USA cInstitute for Immunology and Informatics, University of Rhode Island, 80 Washington Street, Providence, RI 02903, USA d Saint Louis University, St. Louis, MO 63104, USA eLifespan, Rhode Island Hospital, Providence RI, 02903, USA fUniversity of Massachusetts Medical Center, Worcester, MA 01655, USA Abstract While whole killed, whole protein, or live attenuated vaccines were the standard bearers for protective vaccines in the last century, there are concerns about their safety. New vaccine design techniques are contributing to an emphasis on vaccines developed using the minimum essential subset of T- and B-cell epitopes that comprise the “immunome.” We have used bioinformatics sequence analysis tools, epitope-mapping tools, microarrays and high- throughput immunology assays to identify the minimal essential vaccine components for smallpox, tularemia, Helicobacter pylori and tuberculosis vaccines. As will be described in this review, this approach has resulted in the development of four immunome-derived epitope-driven vaccines (ID-EDV); three of these proved protective against viral or bacterial challenge. Protective efficacies of 100% (vaccinia), 90% (H. pylori), and 57% (tularemia) were achieved in HLA-transgenic (humanized) mouse models and the p27 knockout mouse (for H.
    [Show full text]
  • Citrullinated Protein Antibodies in Rheumatoid Arthritis
    ARTHRITIS & RHEUMATOLOGY Vol. 70, No. 12, December 2018, pp 1946–1958 DOI 10.1002/art.40587 © 2018, American College of Rheumatology Affinity Maturation Drives Epitope Spreading and Generation of Proinflammatory Anti–Citrullinated Protein Antibodies in Rheumatoid Arthritis Serra E. Elliott, Sarah Kongpachith, Nithya Lingampalli, Julia Z. Adamska, Bryan J. Cannon, Rong Mao, Lisa K. Blum, and William H. Robinson Objective. Rheumatoid arthritis (RA) is character- were observed (P < 0.01). Shared complementarity-deter- ized by the presence of anti–citrullinated protein antibod- mining region 3 sequence motifs were identified across ies (ACPAs); nevertheless, the origin, specificity, and subjects. A subset of the plasmablast lineages included functional properties of ACPAs remain poorly under- members derived from later time points with divergent stood. The aim of this study was to characterize the evolu- somatic hypermutations that encoded antibodies that tion of ACPAs by sequencing the plasmablast antibody bind an expanded set of citrullinated antigens. Further- repertoire at serial time points in patients with estab- more, these recombinant, differentially mutated plas- lished RA. mablast antibodies formed immune complexes that Methods. Blood samples were obtained at up to 4 stimulated higher macrophage production of tumor serial time points from 8 individuals with established RA necrosis factor (TNF) compared to antibodies represent- who were positive for ACPAs by the anti–cyclic citrulli- ing earlier time point–derived lineage members that were nated peptide test. CD19+CD3ÀIgDÀCD14ÀCD20À less mutated. CD27+CD38++ plasmablasts were isolated by single-cell Conclusion. These findings demonstrate that sorting and costained with citrullinated peptide established RA is characterized by a persistent IgA tetramers to identify ACPA-expressing plasmablasts.
    [Show full text]
  • Integration of Immunome with Disease Gene Network Reveals Pleiotropy and Novel Drug 2 Repurposing Targets
    bioRxiv preprint doi: https://doi.org/10.1101/2019.12.12.874321; this version posted December 13, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Integration of immunome with disease gene network reveals pleiotropy and novel drug 2 repurposing targets 3 Abhinandan Devaprasad1, Timothy RDJ Radstake1, Aridaman Pandit1* 4 1 Center for Translation Immunology, University Medical Center Utrecht, Utrecht, The 5 Netherlands 6 *Correspondence: Aridaman Pandit: [email protected] 7 8 Abstract 9 Immune system is crucial for the development and progression of immune-mediated and non- 10 immune mediated complex diseases. Studies have shown that multiple complex diseases are 11 associated with several immunologically relevant genes. Despite such growing evidence, the 12 effect of disease associated genes on immune functions has not been well explored. Here, we 13 curated the largest immunome (transcriptome profiles of 40 different immune cells) and 14 integrated it with disease gene networks and drug-gene database, to generate a Disease-gene 15 IMmune cell Expression network (DIME). We used the DIME network to: (1) study 13,510 16 genes and identify disease associated genes and immune cells for >15,000 complex diseases; 17 (2) study pleiotropy between various phenotypically distinct rheumatic and other non- 18 rheumatic diseases; and (3) identify novel targets for drug repurposing and discovery. We 19 implemented DIME as a tool (https://bitbucket.org/systemsimmunology/dime) that allows 20 users to explore disease-immune-cell associations and disease drug networks to pave way for 21 future (pre-) clinical research.
    [Show full text]
  • Immunome Discovery Engine Simultaneously Identifies Antibodies and Their Antigen Targets by Interrogating the Patient’S Memory B Cells in an Unbiased Manner
    Developing Antibody‐Based Therapeutics by Unlocking the Human Memory B Cell Response Immunome, Inc. 665 Stockton Drive, Suite 300 Exton, PA 19341 October 26, 2020 610.321.3700 www.immunome.com Forward Looking Statements This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. The Company intends forward-looking terminology such as “believes,” “anticipates,” “plans,” “may,” “intends,” “will,” “should,” “expects,” and similar expressions to identify forward-looking statements. Further, forward-looking statements include, but are not limited to, statements regarding the Company’s financial position, strategy, business plans, expectations regarding the timing and achievement of its product candidate development activities and ongoing and planned preclinical studies and clinical trials, plans and expectations for future operations and research and development initiatives. Any statements contained herein that are not statements of historical facts may be deemed to be forward-looking statements. These forward-looking statements involve risks and uncertainties, including regarding the Company’s expectation that it will incur net losses for the foreseeable future, and that it may never be profitable; its need for additional funding; the timing and success of preclinical studies and clinical trials it conducts; the ability to obtain and maintain regulatory approval of its product candidates; the ability to commercialize its product candidates; its ability to compete in the marketplace; developments relating to the COVID-19 pandemic; its ability to obtain and maintain intellectual property protection for its product candidates; and its ability to manage growth. These or other risks or uncertainties may cause the Company’s actual results to differ materially from any forward-looking statements.
    [Show full text]
  • An Integrated Genomic and Immunoinformatic Approach to H
    University of Rhode Island DigitalCommons@URI Institute for Immunology and Informatics Faculty Institute for Immunology and Informatics (iCubed) Publications 2011 An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design Matthew Ardito Joanna Fueyo See next page for additional authors Creative Commons License This work is licensed under a Creative Commons Attribution 3.0 License. Follow this and additional works at: https://digitalcommons.uri.edu/immunology_facpubs Terms of Use All rights reserved under copyright. Citation/Publisher Attribution Ardito, M., Fueyo, J., Tassone, R., Terry, F., DaSilva, K., Zhang, S., Martin, W., De Groot, A. S., Moss, S. F., & Moise, L. (2011). An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design. Immunome Research, 7(2). Available at: http://dx.doi.org/10.4172/1745-7580.1000049 This Article is brought to you for free and open access by the Institute for Immunology and Informatics (iCubed) at DigitalCommons@URI. It has been accepted for inclusion in Institute for Immunology and Informatics Faculty Publications by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. Authors Matthew Ardito, Joanna Fueyo, Ryan Tassone, Frances Terry, Kristin DaSilva, Songhua Zhang, William Martin, Anne S. De Groot, Steven F. Moss, and Leonard Moise This article is available at DigitalCommons@URI: https://digitalcommons.uri.edu/immunology_facpubs/32 Ardito et al. Immunome Research 2011, 7:2:1 http://www.immunome-research.net/ RESEARCH Open Access An Integrated Genomic and Immunoinformatic Approach to H. pylori Vaccine Design Matthew Ardito1, Joanna Fueyo2¶, Ryan Tassone1, Frances Terry1, Kristen DaSilva3, Songhua Zhang4, Wil- liam Martin1, Anne S.
    [Show full text]
  • RESEARCH Open Access
    Alamyar et al. Immunome Research 2012, 8:1:2 http://www.immunome-research.net/ RESEARCH Open Access IMGT/HIGHV-QUEST: THE IMGT® WEB PORTAL FOR IMMUNOGLOBULIN (IG) OR ANTIBODY AND T CELL RECEPTOR (TR) ANALYSIS FROM NGS HIGH THROUGHPUT AND DEEP SEQUENCING Eltaf Alamyar 1, Véronique Giudicelli 1, Shuo Li 2, Patrice Duroux 1, Marie-Paule Lefranc1§ ABSTRACT BACKGROUND The number of antigen receptors, immunoglobulins (IG) or antibodies and T cell receptors (TR) of the adap- tive immune response in vertebrates with jaws is almost unlimited (2.1012 per individual in humans). This huge diversity results from complex mechanisms in the synthesis of the variable (V) domains, that include DNA molecular rearrangements of the V, diversity (D) and joining (J) genes, N-diversity at the V-(D)-J junc- tions and, for IG, somatic hypermutations. The specificity of the V domains is conferred by the complemen- tarity determining regions (CDR) and more particularly the CDR3. IMGT®, the international ImMunoGeneT- ics information system®, has developed online tools that provide a detailed and accurate sequence analy- sis of the V domains (IMGT/V-QUEST) and CDR3 (IMGT/JunctionAnalysis), based on IMGT-ONTOLOGY. However online analyses are limited to 50 sequences per batch. The challenge was to provide identical high quality analysis for the huge number of sequences obtained by Next Generation Sequencing (NGS) high throughput and deep sequencing. Results IMGT® has developed IMGT/HighV-QUEST that analyses up to 150,000 IG or TR V domain sequences per batch and performs statistical analysis on the results of up to 450,000 sequences.
    [Show full text]
  • A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data
    A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Ig Sequencing Data This information is current as Ang Cui, Roberto Di Niro, Jason A. Vander Heiden, Adrian of October 1, 2021. W. Briggs, Kris Adams, Tamara Gilbert, Kevin C. O'Connor, Francois Vigneault, Mark J. Shlomchik and Steven H. Kleinstein J Immunol published online 5 October 2016 http://www.jimmunol.org/content/early/2016/10/05/jimmun ol.1502263 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2016/10/05/jimmunol.150226 Material 3.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on October 1, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2016 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published October 5, 2016, doi:10.4049/jimmunol.1502263 The Journal of Immunology A Model of Somatic Hypermutation Targeting in Mice Based on High-Throughput Immunoglobulin Sequencing Data Ang Cui,* Roberto Di Niro,† Jason A. Vander Heiden,* Adrian W.
    [Show full text]
  • Immunomic Analysis of Human Sarcoma
    Immunomic analysis of human sarcoma Sang-Yull Lee*, Yuichi Obata†, Masahiro Yoshida‡, Elisabeth Stockert*, Barbara Williamson*, Achim A. Jungbluth*, Yao-Tseng Chen*§, Lloyd J. Old*, and Matthew J. Scanlan*¶ *Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan–Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; †RIKEN Bioresource Center, RIKEN Tsukuba Institute, 3-1-1 Koyadai Tsukuba 305-0074, Japan; ‡Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan; and §Department of Pathology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021 Contributed by Lloyd J. Old, December 30, 2002 The screening of cDNA expression libraries from human tumors (17) that elicit spontaneous cellular (18) and humoral immune with serum antibody (SEREX) has proven to be a powerful method (19) responses in some cancer patients. Because of their tissue- for identifying the repertoire of tumor antigens recognized by the restricted expression and immunogenicity, CT antigens are immune system of cancer patients, referred to as the cancer potential targets for vaccine-based immunotherapies. In general, immunome. In this regard, cancer͞testis (CT) antigens are of CT antigens are expressed in 20–40% of specimens from a given particular interest because of their immunogenicity and restricted tumor type (18, 20). One exception to this is synovial sarcoma, expression patterns. Synoivial sarcomas are striking with regard to in which 80% of specimens express the CT antigens, NY-ESO-1 CT antigen expression, with >80% of specimens homogeneously (21), and MAGE (22). expressing NY-ESO-1 and MAGE-A3. In the present study, 54 The current study examines the humoral immune response of sarcoma patients were tested for serum antibodies to NY-ESO-1, sarcoma patients to sarcoma and testicular antigens.
    [Show full text]
  • Protein-Based Immunome Wide Association Studies (PIWAS) for the Discovery of Significant Disease-Associated Antigens
    bioRxiv preprint doi: https://doi.org/10.1101/2020.03.18.997759; this version posted March 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Protein-based Immunome Wide Association 2 Studies (PIWAS) for the discovery of 3 significant disease-associated antigens 4 Winston A. Haynes1, Kathy Kamath1, Patrick S. Daugherty1, John C. Shon1,* 5 1Serimmune, Inc. Santa BarBara, CA, USA. 6 *Corresponding author: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.03.18.997759; this version posted March 20, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 7 Abstract 8 Identification of the antigens associated with antiBodies is vital to understanding immune 9 responses in the context of infection, autoimmunity, and cancer. Discovering antigens at a 10 proteome scale could enable Broader identification of antigens that are responsiBle for 11 generating an immune response or driving a disease state. Although targeted tests for known 12 antigens can Be straightforward, discovering antigens at a proteome scale using protein and 13 peptide arrays is time consuming and expensive. We leverage Serum Epitope Repertoire 14 Analysis (SERA), an assay Based on a random Bacterial display peptide liBrary coupled with NGS, 15 to power the development of Protein-Based Immunome Wide Association Study (PIWAS).
    [Show full text]
  • Immunome Research Biomed Central
    Immunome Research BioMed Central Research Open Access Using the natural evolution of a rotavirus-specific human monoclonal antibody to predict the complex topography of a viral antigenic site Brett A McKinney*1, Nicole L Kallewaard2, James E Crowe Jr3 and Jens Meiler4 Address: 1Department of Genetics, University of Alabama School of Medicine, 720 20th Street South, Birmingham, 35294, USA, 2Division of Infectious Diseases, Children's Hospital of Philadelphia, 34th Street and Civic Center Boulevard, Philadelphia, 19104 USA, 3Program in Vaccine Sciences, Departments of Microbiology and Immunology and Pediatrics, Vanderbilt University Medical Center, 21st Avenue South and Garland Avenue, Nashville, 37232, USA and 4Center for Structural Biology, Department of Chemistry, Vanderbilt University, 2201 West End Avenue, Nashville, 37232, USA Email: Brett A McKinney* - [email protected]; Nicole L Kallewaard - [email protected]; James E Crowe - [email protected]; Jens Meiler - [email protected] * Corresponding author Published: 18 September 2007 Received: 4 June 2007 Accepted: 18 September 2007 Immunome Research 2007, 3:8 doi:10.1186/1745-7580-3-8 This article is available from: http://www.immunome-research.com/content/3/1/8 © 2007 McKinney et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Understanding the interaction between viral proteins and neutralizing antibodies at atomic resolution is hindered by a lack of experimentally solved complexes. Progress in computational docking has led to the prediction of increasingly high-quality model antibody-antigen complexes.
    [Show full text]
  • Supplementary Material to Andrés Corral-Lugo, Mireia López-Siles
    Supplementary material to Identification and analysis of unstructured, linear B-cell epitopes in SARS-CoV-2 virion proteins for vaccine development Andrés Corral-Lugo, Mireia López-Siles, Daniel López, Michael J. McConnell and Antonio J. Martín-Galiano 1 Supplementary Data S1. Conservation of B-cell epitopes in S, E, M and N protein across coronavirus species. Independent sequence alignments between uBCELs/BCEH of SARS-CoV-2, and equivalent sequences in SARS-CoV and three bat coronavirus samples: bat-SL-CoVZXC21, bat-SL-CoVZC45 and RaTG13. For clarity, SARS-CoV and SARS- CoV-2 headers are in bold letters. Residues in uBCEs are in capital letters while the rest of the loop is in lowercase. Identical residues to SARS-CoV-2 sequences are highlighted in green. Deletions are indicated with dashes. S protein uBCEL-S1 SARS-CoV 20_ddvqaPNYTQHTS_32 Bat-SL-CoVZXC21 17_-dltGRTPLNPNY_28 Bat-SL-CoVZC45 17_vnltGRTPLNPNY_29 RaTG13 15_vnlttRTQLPPAY_27 SARS-CoV-2 15_vnlttRTQLPPAY_27 : uBCEL-S2 SARS-CoV 72_in-------HTFGNpvip_82 Bat-SL-CoVZXC21 68_lttN-NAATKRTDNpild_84 Bat-SL-CoVZC45 69_lttN-NAATKRTDNpild_85 RaTG13 68_ihvSGTNGIKRFDNpvlp_85 SARS-CoV-2 68_ihvSGTNGTKRFDNpvlp_85 : : .**:: uBCEL-S3 SARS-CoV 389_vkGDDVRQIAPgqtgviadynyklpddf_416 Bat-SL-CoVZXC21 397_irFSEVRQVAPgqtgviadynyklpddf_424 Bat-SL-CoVZC45 398_irFSEVRQVAPgqtgviadynyklpddf_425 RaTG13 402_itGDEVRQIAPgqtgkiadynyklpddf_429 SARS-CoV-2 402_irGDEVRQIAPgqtgkiadynyklpddf_429 : .:***:****** ************ uBCEL-S4 SARS-CoV 427_NIDATStgnyn_437 Bat-SL-CoVZXC21 435_KQDT-----gh_440 Bat-SL-CoVZC45 436_KQDV-----gn_441
    [Show full text]