Immunome

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The immunome is the set of genes that code for proteins which constitute the immune system, excluding those that are widespread in other cell types, and not involved in the immune response itself. [1] [2] It is further defined as the set of peptides derived from the proteome that interact with the immune system. [3] There are numerous ongoing efforts to characterize and sequence the immunomes of humans, mice, and elements of non-human primates. Typically, immunomes are studied using immunofluorescence microscopy to determine the presence and activity of immune-related enzymes and pathways. [4] Practical applications for studying the immunome include vaccines, therapeutic proteins, and further treatment of other diseases. [3] [5] The study of the immunome falls under the field of immunomics.

Contents

Etymology

The word immunome is a portmanteau of the words "immune" and "chromosome." See omics for a further discussion.

Efforts to characterize

The exact size of the human immunome is currently unknown and has been a topic of study for decades. [6] However, the amount of information it encodes is said to exceed the size of the human genome by several orders of magnitude due to, at least in part, somatic hypermutation and junctional diversity. [7] [8] There are several ongoing efforts to characterize the immunomes of humans and other species. [9] [10] [11] [12]

One major effort, launched in 2016, is a collaborative project between The Human Vaccines Project, Vanderbilt University Medical Center, and Illumina, Inc. [9] This project is entitled the Human Immunome Program and its goal is to decipher the complete collection of B and T immune cell receptors from the human population. [13] Thousands of individuals will need to be studied in order to meet this goal, and they will need to represent different ages, genders, ethnicities, and geographical origins. Furthermore, people with diseases and people who have undergone vaccination will need to be studied as well. [9] The results of the program will be shared as an open-sourced database. [14] The sequencing project will continue until no new unique sequences occur within the B and T cell receptors and is expected to take ten years. [15]

Similarly, there is a research project called the Immunological Genome Project whose stated goal is to generate "a complete microarray dissection of gene expression and its regulation in the immune system of the mouse". In other words, the project is trying to define and characterize the immunome of the mouse. This project is primarily intended to function as a primary resource and the researchers actively accept suggestions from the community. The project team consists of more than 20 research labs, all working on various aspects of the project, including studying T cells, B cells, and dendritic cells, along with many other types of cells within the mouse immunome. The project has been ongoing since 2008. [10]

Efforts are also being made to characterize aspects of non-human immunomes, particularly non-human primates because of their genetic similarity to humans. [11] [12]

Methods of study

In order to gain useful knowledge about the immunome and its characteristics, the cells and components of the immune system must be phenotyped in a quick and pragmatic manner. There are hundreds of known cell types within the immune system and the possibility of detecting and characterizing them without the use of recent advances in immunophenotyping technology was remote because large amounts of an individual's blood would have been required. This outdated method is called low-dimensional immunophenotyping. However, high-dimensional immunophenotyping is now a possibility. The types of high-dimensional immunophenotyping can be broadly grouped into two categories: the use of isotopes of lanthanide and the use of fluorophores. These advanced technologies allow for up to 100 parameters to be measured at one time. [4]

Applications

There are potentially far-reaching applications for studying the immunome. Some scientists believe that knowledge gained from the immunome could lead to the discovery of differences in the absolute number of T cell epitopes, and could reveal antigenic relationships between different but immunologically similar pathogens, potentially unlocking autoimmune disease therapies and organ transplantation. [3]

Immunome investigation has proven useful in determining the symptoms and potential causes of pulmonary fibrosis on a molecular level. [16]

The development of vaccines is also an application of immunome study as shown by Carlos F. Suárez and his colleagues. They were able to find components of a malaria vaccine that could be readily used in humans as a result of having characterized the cell surface receptor of an immune cell from an owl monkey. These monkeys have been shown to be highly susceptible to human malaria, so they serve as a good model for the disease. [17] It could also be possible to develop an influenza vaccine that would provide protection from several strains of the virus. [18]

Furthermore, analyzation of the immunomes of non-human primates and other species can reflect the evolutionary history of species as shown by David F. Plaza and his colleagues. This immunome data can also be helpful when testing antibody therapies on non-human primates to ensure they are safe for humans. This can be accomplished by being able to interpret results in the context of the slight differences in ortholog structure between the human and non-human primate immunomes. [19]

Databases

There are a number of databases corresponding to the different facets of the human immunome and the immunomes of other species. [20]

Immunome Knowledge Base (IKB)

An effort is being made to assemble immunological information into a singular database called the Immunome Knowledge Base(IKB). The two scientists behind the effort, Csaba Ortutay & Mauno Vihinen, have integrated data from three separate databases into IKB. These three databases, Immunome, ImmTree, and ImmunomeBase, all have separate, but related information pertaining to the immunome. Immunome contains entries to official gene names according to the HUGO Gene Nomenclature Committee, alternative names, and locations of genes on the chromosomes. ImmTree contains entries related to the molecular evolution of the immune system, including orthologous genes and phylogenetic trees. Finally, ImmunomeBase is a multi-species database related to immunity. Altogether, as of 2009, IKB has entries for more than 100,000 data items, including 893 entries for genes in the immunome. [1]

Immune Epitope Database (IEDB)

This database serves as a resource for data on antibody and T cell epitopes studied in humans, non-human primates, and other species as it relates to disease, allergies, autoimmunity, and transplantation. The database also has tools to assist in the prediction and analysis of epitopes. [21]

Immunome Database for Marsupials and Monotremes (IDMM)

This database has data for every known marsupial and monotreme immune gene. It serves as a resource for immunologists and researchers studying the evolution of mammalian immunity. [22]

Immunology Database and Analysis Portal (ImmPort)

A database developed for the purpose of promoting the re-use of immunological data. It is a partnership between researchers at the University of California-San Francisco, Stanford University, the University of Buffalo, the Technion - Israel Institute of Technology, and Northrop Grumman. It encompasses results from over 400 studies related to immunology. [23]

Immunological Genome Project (ImmGen)

This database is a public resource containing the data relating to the study of the immune system of the mouse. [10]

Other databases

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

<span class="mw-page-title-main">Antibody</span> Protein(s) forming a major part of an organisms immune system

An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen with diverse chemical compositions from molecules. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly.

<span class="mw-page-title-main">Immune system</span> Biological system protecting an organism against disease

The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as cancer cells, parasitic worms, and also objects such as wood splinters, distinguishing them from the organism's own healthy tissue. Many species have two major subsystems of the immune system. The innate immune system provides a preconfigured response to broad groups of situations and stimuli. The adaptive immune system provides a tailored response to each stimulus by learning to recognize molecules it has previously encountered. Both use molecules and cells to perform their functions.

<span class="mw-page-title-main">DNA vaccine</span> Vaccine containing DNA

A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response.

<span class="mw-page-title-main">Autoimmunity</span> Immune response against an organisms own healthy cells

In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". Prominent examples include celiac disease, diabetes mellitus type 1, Henoch–Schönlein purpura, systemic lupus erythematosus, Sjögren syndrome, eosinophilic granulomatosis with polyangiitis, Hashimoto's thyroiditis, Graves' disease, idiopathic thrombocytopenic purpura, Addison's disease, rheumatoid arthritis, ankylosing spondylitis, polymyositis, dermatomyositis, and multiple sclerosis. Autoimmune diseases are very often treated with steroids.

<span class="mw-page-title-main">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

The cluster of differentiation is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells. In terms of physiology, CD molecules can act in numerous ways, often acting as receptors or ligands important to the cell. A signal cascade is usually initiated, altering the behavior of the cell. Some CD proteins do not play a role in cell signaling, but have other functions, such as cell adhesion. CD for humans is numbered up to 371.

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<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system is a complex of genes on chromosome 6 in humans that encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

In academia, computational immunology is a field of science that encompasses high-throughput genomic and bioinformatics approaches to immunology. The field's main aim is to convert immunological data into computational problems, solve these problems using mathematical and computational approaches and then convert these results into immunologically meaningful interpretations.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

Molecular mimicry is the theoretical possibility that sequence similarities between foreign and self-peptides are enough to result in the cross-activation of autoreactive T or B cells by pathogen-derived peptides. Despite the prevalence of several peptide sequences which can be both foreign and self in nature, just a few crucial residues can activate a single antibody or TCR. This highlights the importance of structural homology in the theory of molecular mimicry. Upon activation, these "peptide mimic" specific T or B cells can cross-react with self-epitopes, thus leading to tissue pathology (autoimmunity). Molecular mimicry is one of several ways in which autoimmunity can be evoked. A molecular mimicking event is more than an epiphenomenon despite its low probability, and these events have serious implications in the onset of many human autoimmune disorders.

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<span class="mw-page-title-main">CD7</span> Mammalian protein found in humans

CD7 is a protein that in humans is encoded by the CD7 gene.

Immunomics is the study of immune system regulation and response to pathogens using genome-wide approaches. With the rise of genomic and proteomic technologies, scientists have been able to visualize biological networks and infer interrelationships between genes and/or proteins; recently, these technologies have been used to help better understand how the immune system functions and how it is regulated. Two thirds of the genome is active in one or more immune cell types and less than 1% of genes are uniquely expressed in a given type of cell. Therefore, it is critical that the expression patterns of these immune cell types be deciphered in the context of a network, and not as an individual, so that their roles be correctly characterized and related to one another. Defects of the immune system such as autoimmune diseases, immunodeficiency, and malignancies can benefit from genomic insights on pathological processes. For example, analyzing the systematic variation of gene expression can relate these patterns with specific diseases and gene networks important for immune functions.

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C-ImmSim started, in 1995, as the C-language "version" of IMMSIM, the IMMune system SIMulator, a program written back in 1991 in APL-2 by the astrophysicist Phil E. Seiden together with the immunologist Franco Celada to implement the Celada-Seiden model. The porting was mainly conducted and further developed by Filippo Castiglione with the help of few other people.

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References

  1. 1 2 Ortutay, Csaba; Vihinen, Mauno (2009). "Immunome Knowledge Base (IKB): An integrated service for immunome research". BMC Immunology. 10 (3): 3. doi: 10.1186/1471-2172-10-3 . PMC   2632617 . PMID   19134210.
  2. ↑ "IAVI Report - Prepping for the Immunome". Iavireport.org. Retrieved April 25, 2016.
  3. 1 2 3 De Groot, Anne (1 December 2009). "Exploring the immunome: A brave new world for human vaccine development". Human Vaccines. 5 (12): 790–793. doi:10.4161/hv.10683. PMC   2919815 . PMID   20009527.
  4. 1 2 Biancotto, A; McCoy, JP (2014). "Studying the Human Immunome: The Complexity of Comprehensive Leukocyte Immunophenotyping". Curr. Top. Microbiol. Immunol. Current Topics in Microbiology and Immunology. 377: 23–60. doi:10.1007/82_2013_336. ISBN   978-3-642-54826-0. PMC   4184245 . PMID   23975032.
  5. ↑ Snyder, William (22 September 2017). "Cracking the Code of the Immune System". Vanderbilt Medicine Magazine. Vanderbilt University. Retrieved 1 May 2020.[ permanent dead link ]
  6. ↑ De Groot, Anne; Moise, Leonard; McMurry, Julie; Martin, William (2009). "Epitope-Based Immunome-Derived Vaccines: A Strategy for Improved Design and Safety". Clinical Applications of Immunomics. New York, NY: Springer. pp. 39–69. doi:10.1007/978-0-387-79208-8_3. ISBN   978-0-387-79208-8. S2CID   61847889.
  7. ↑ Briney, Bryan; Inderbitzin, Anne; Joyce, Collin; Burton, Dennis (21 January 2019). "Commonality despite exceptional diversity in the baseline human antibody repertoire". Nature. 566 (7744): 393–397. Bibcode:2019Natur.566..393B. doi:10.1038/s41586-019-0879-y. PMC   6411386 . PMID   30664748.
  8. ↑ Soto, Cinque; Bombardi, Robin; Branchizio, Andre; Kose, Nurgun; Matta, Pranathi; Sevy, Alexander; Sinkovits, Robert; Gilchuk, Pavlo; Finn, Jessica; Crowe Jr, James (13 February 2019). "High frequency of shared clonotypes in human B cell receptor repertoires". Nature. 566 (7744): 398–402. Bibcode:2019Natur.566..398S. doi:10.1038/s41586-019-0934-8. PMC   6949180 . PMID   30760926.
  9. 1 2 3 Snyder, Bill. "Vanderbilt and Human Vaccines Project launch initial studies to decode the human immune system". Vanderbilt University Medical Center. Vanderbilt University. Retrieved 1 May 2020.
  10. 1 2 3 "Immunological Genome Project". Immunological Genome Project. ImmGen Project. Retrieved 1 May 2020.
  11. 1 2 Moncada, Camilo; Guerrero, Eduar; Cardenas, Paula; Suarez, Carlos; Patarroyo, Manuel E; Patarroyo, Manuel A (2005). "The T-cell receptor in primates: identifying and sequencing new owl monkey TRBV gene sub-groups". Immunogenetics. 57 (1–2): 42–52. doi:10.1007/s00251-004-0758-y. PMID   15711805. S2CID   19979972.
  12. 1 2 Cardenas, Paula; Suarez, Carlos; Martinez, Pilar; Patarroyo, Manuel E; Patarroyo, Manuel A (2005). "MHC class I genes in the owl monkey: mosaic organisation, convergence and loci diversity". Immunogenetics. 56 (11): 818–832. doi:10.1007/s00251-004-0751-5. PMID   15654599. S2CID   25274078.
  13. ↑ Wooden, SL; Koff, WC (2018). "The Human Vaccines Project: Towards a comprehensive understanding of the human immune response to immunization". Human Vaccines & Immunotherapeutics. 14 (9): 2214–2216. doi: 10.1080/21645515.2018.1476813 . PMC   6183335 . PMID   6183335.
  14. ↑ "The Human Vaccines Project, Vanderbilt And Illumina Join Forces To Decode The Human Immunome". PR Newswire (Press release). PR Newswire Association LLC. Retrieved 1 May 2020.
  15. ↑ "Human Immunome Program". clinicaltrials.gov. US National Institute of Health. Retrieved 1 May 2020.
  16. ↑ El-Chemaly, Souheil; Cheung, Foo; Kotilarov, Yuri; O'Brien, Kevin; Gahl, William; Chen, Jinguo; Perl, Shira; Biancotto, Angelique; Gochuico, Bernadette (31 January 2018). "The Immunome in Two Inherited Forms of Pulmonary Fibrosis". Front Immunol. 9 (76): 76. doi: 10.3389/fimmu.2018.00076 . PMC   5797737 . PMID   29445374.
  17. ↑ Suarez, Carlos; Pabon, Laura; Barrera, Ana; Aza-Conde, Jorge; Patarroyo, Manuel Alfonso; Patarroyo, Manuel Elkin (30 September 2017). "Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans". Biochemical and Biophysical Research Communications. 491 (4): 1062–1069. doi:10.1016/j.bbrc.2017.08.012. PMID   28782517.
  18. ↑ Dumiak, Michael (2014). "Prepping for the immunome". IAVI Report. 18 (3). International AIDS Vaccine Initiative: 14–7. PMID   25401194.
  19. ↑ Plaza, David F; Gomez, Manuel; Patarroyo, Manuel (31 October 2019). "NHP-immunome: A translational research-oriented database of non-human primate immune system proteins". Cellular Immunology. 347: 103999. doi: 10.1016/j.cellimm.2019.103999 . PMID   31733823.
  20. 1 2 Breuer. "Immunology Relevant Databases". InnateDB.
  21. ↑ Immune Epitope Database and Analysis Resource. National Institutes of Health in the Department of Health and Human Services http://www.iedb.org/.{{cite web}}: Missing or empty |title= (help)
  22. ↑ Wong, Emily SW; Papenfuss, Anthony T; Belov, Katherine (2011). "Immunome database for marsupials and monotremes". BMC Immunology. 12: 48. doi: 10.1186/1471-2172-12-48 . PMC   3173380 . PMID   21854560.
  23. ↑ "ImmPort". Archived from the original on 2020-04-17. Retrieved 2020-05-08.
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