IEDB Inclusion Criteria

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Inclusion/Exclusion Criteria

All articles and epitopes must meet inclusion criteria in order to be included in the database.

Relevant Experimental Data

Experimental Data

The reference must report original and experimental epitope-related data.

  • Computer derived predictions without functional experimental data will not be included in the database.
  • Sequence analysis of defined epitopes will not be included in the database unless novel information is provided (e.g., identification of anchor residues).
  • Reviews and meta analysis will not be included in the database.
  • Data not shown is not curated.
  • Personal communication is not sufficient for curation.
  • When encountering data from previous publications which are included in figures or tables, the curator should determine if the previous record was curated and if it was not, the PMID should be sent to the Document Specialist to be included in the database.

Scope and Exclusions

The experimental data must fall within the scope of the database.

Relevant data includes:

  • MHC binding data
  • Epitope elution from MHC (Naturally processed MHC ligands)
  • T cell responses to an epitope (including NK T cells)
  • B cell/antibody responses to an epitope

Certain categories of experimental data will be specifically excluded from the database.

Exclusion: NK Epitopes

Epitopes that are recognized by Natural Killer cells (non-T cell) will be excluded from the database. Please note: NK T cell epitopes/ligands will be included (as noted in section (#Scope and Exclusions).

Exclusion: Non-Immunological Interpretation of "Epitope"

Experimental data describing "epitopes" in non-immunological contexts will not be included in the database. For example, the structures that are in contact in protein-protein interactions are sometimes referred to as an epitope. This interpretation of "epitope" will not be included in the database.

Exclusion: Epitope Tags

References discussing epitope tags utilized as a technical tool for immunoprecipitation, purification, and similar experiments will be excluded from the database.

Exclusion: Superantigen

References discussing superantigens in the context of peptide-MHC-super antigen complexes will be excluded from the database. However, B cell/antibody responses to superantigens (especially Staphylococcus enterotoxin B (SEB), a NIAID Category B priority pathogen) will be curated.

Important Note: In the event superantigen is used as part of an assay to stabilize the interaction of an epitope with MHC, the epitope studied is curatable and should be captured.

Exclusion: TCR Antagonism

Data related to TCR antagonism will not be curated. Author stated TCR antagonism will not be curated, however, TCR competition not specifically labeled as TCR antagonism by the authors will be curated. TCR antagonism used in an MHC binding inhibition assay will be captured as an MHC binding assay.

Exclusion: Antigen Processing

Data concerning the processing of antigens generated in order to study the effects of variables on processing rather than on the study of an epitope (i.e. the epitope is irrelevant) are not to be included in the database unless the identification of a novel epitope is demonstrated.


Epitopes Relevant to IEDB

Length/Mass Restrictions

Peptidic Epitopes

Table 1. Length/Mass Restrictions
Epitope Class Uncuratable Epitopic Region (# residues) Epitope
(# residues)
B-cell > 5 kDa or 50 amino acids 12 - 50 1 ≤ x ≤ 11
Class I > 5 kDa or 50 amino acids 12 - 50 7 ≤ x ≤ 11
Class II > 5 kDa or 50 amino acids 16 - 50 7 ≤ x ≤ 15

The database will only include epitopes of less than 50 residues in either a linear or conformational sequence.


Important Exception: Epitopes greater than 50 residues will be curated for certain pathogens including Botulinum toxin and anthrax epitopes.

A region or fragment of >50aa from B. anthracis and C. botulinum will be curated as an epitopic region in the following cases:

Figure 1. Curation of Botulinum toxin and Anthrax epitopes.



Non-peptidic epitopes

For non-peptidic epitopes, the mass restriction is to be less than 5000 Daltons to be included in the database.

  • For Antibody/B Cell and Class I epitopes if the size is 1100 Dalton or less, the epitope should be designated as an Exact Epitope.
  • For linear Class II epitopes, select Exact Epitope if the sequence is 1500 Dalton or less in length.

Well-Characterized Epitopes

To broaden the spectrum of information in the database, we previously excluded the repeated curation of epitopes once 10 key references have been included in the database. The original articles describing the epitope, MHC restriction data, antibody responses, and articles containing novel information regarding the epitope were included in the approximately 10 references.

The concept of well-characterized/blacklisted has been eliminated. Going forward, we will avoid curating papers that focus on exploring strategies to enhance well characterized epitope's immunogenicity. These papers use well-characterized peptides to evaluate variables such as alternative immunogen constructs (MAPS/vectors) or adjuvants.

All references should be evaluated for novelty such as providing a new assay type, host, MHC restriction, or outcome for the given epitope.

  • When well-characterized epitopes are studied in a novel host in terms of the MHC, TCR, antibody, or otherwise, the reference will be included in the database.
  • When well-characterized epitopes are used as controls they will not be curated. However, when the well-characterized epitope is used as a reference for a novel epitope from the same source protein, the well-characterized epitope will also be captured.
  • When a reference describes a well-characterized epitope in addition to other curatable epitopes, all of the epitopes from the reference will be captured.
  • At the curators/EC discretion, papers describing new/additional original data relating to these epitopes can and will be curated. For example, if the paper make a novel discovery about the epitope.
  • all human data should be captured
  • always ask before deciding to not curate any reference


Curation exception: If a manuscript ONLY contains any single assay that has already been curated multiple times from one or more of the following epitopes, do not curate the manuscript. If the manuscript contains such data and additional novel or rare data for these epitopes or contains additional epitopes, then curate the entire manuscript as usual.

Human herpesvirus 5 NLVPMVATV TPRVTGGGAM

Influenza A virus ASNENMETM SSLENFRAYV GILGFVFTL

Human herpesvirus 4 GLCTLVAML CLGGLLTMV FLRGRAYGL

Hepatitis C virus CINGVCWTV KLVALGINAV

Human herpesvirus 1 SSIEFARL

Gallus gallus SIINFEKL

LCMV KAVYNFATM

HIV/SIV

References describing only epitopes derived from HIV/SIV will not be included in the database. However, when a manuscript describes epitopes from other relevant sources as well as HIV/SIV, all of the epitopes in the manuscript will be captured.

Curation Prioritization

Epitope curation should be conducted in the following priority order:

A) NIAID Category A, B, and C priority pathogens and toxins:

The complete list of NIAID Category A, B, and C priority pathogens and toxins can be found at the following URL: http://www2.niaid.nih.gov/biodefense/bandc_priority.htm.

NIAID – Category A

Bacillus anthracis (anthrax)

Clostridium botulinum

Yersinia pestis

Variola major (smallpox) and other pox viruses

Francisella tularensis (tularemia)

Viral hemorrhagic fevers

Arenaviruses

LCM, Junin virus, Machupo virus, Guanarito virus

Lassa Fever

Bunyaviruses

Hantaviruses

Rift Valley Fever

Flaviruses

Dengue

Filoviruses

Ebola

Marburg

NIAID – Category B

Burkholderia pseudomallei

Coxiella burnetii (Q fever)

Brucella species (brucellosis)

Burkholderia mallei (glanders)

Ricin toxin (from Ricinus communis)

Epsilon toxin of Clostridium perfringens

Staphylococcus enterotoxin B

Typhus fever (Rickettsia prowazekii)

Food and Waterborne Pathogens

Bacteria

Diarrheagenic E.coli

Pathogenic Vibrios

Shigella species

Salmonella

Listeria monocytogenes

Campylobacter jejuni

Yersinia enterocolitica)

Viruses (Caliciviruses, Hepatitis A)

Protozoa

Cryptosporidium parvum

Cyclospora cayatanensis

Giardia lamblia

Entamoeba histolytica

Toxoplasma

Microsporidia

Additional viral encephalitides

West Nile Virus

LaCrosse

California encephalitis

VEE

EEE

WEE

Japanese Encephalitis Virus

Kyasanur Forest Virus

NIAID – Category C

Tickborne hemorrhagic fever viruses

Crimean-Congo Hemorrhagic fever virus

Tickborne encephalitis viruses

Yellow fever

Multi-drug resistant TB

Influenza

Other Rickettsias

Rabies

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV)

B) Emerging and Re-emerging pathogens:

Pathogens newly recognized in the past two decades

Acanthamebiasis

Australian bat lyssavirus

Babesia, atypical

Bartonella henselae

Ehrlichiosis

Encephalitozoon cuniculi

Encephalitozoon hellem

Enterocytozoon bieneusi

Helicobacter pylori

Hendra or equine morbilli virus

Hepatitis C

Hepatitis E

Human herpesvirus 8

Human herpesvirus 6

Lyme borreliosis

Microsporidia

Parvovirus B19

Coronaviruses/Severe Acute Respiratory Syndrome (SARS)

Re-emerging Pathogens

Enterovirus 71

Prion diseases

Streptococcus, group A

Staphylococcus aureus

  • Coccidioides immitis

C) Transplant rejection antigens and other alloantigens, Allergens, and Self antigens involved in autoimmunity

D) Infectious diseases not listed above under sections (#Curation Prioritization) A) and B)


Well represented categories

Due to the redundant nature of certain categories, these categories are currently down prioritized:


A) If a manuscript has a 3D structure/PDB ID, we will curate it if it belongs to any category other than Autoimmune BETAAM

B) If a manuscript is found by the usual pubmed query OR by the google scholar tetramer query, we will curate it if it belongs to any category other than

HIV, Cancer, Others, or the following categories: Autoimmune BETAAM

Transplant GAL

Autoimmune Lupus APL

Autoimmune Multiple Sclerosis MOG35

Autoimmune Multiple Sclerosis P139

Autoimmune Multiple Sclerosis MBP78

Allergen Other Allergen DNP

Autoimmune Multiple Sclerosis Ac1-9

Autoimmune Rheumatoid Arthritis C260

Minimal Data Requirements

The reference must contain information for all required fields for at least one epitope in order to be included in the database. There are five major categories containing twenty-six fields. One set of data from each category must be available. These fields are highlighted in yellow in the data dictionary available in the Curation Network folder: (\\Curation\Docs\DataDictionary\). The required fields are listed in Table 3

Table 3 Required Fields
# Section Classification Field Name Comments
1 a   Reference -Journal Article PubMed ID At least one set of fields from Category # 1 (1a, 1b or 1c) has to be filled out.
  b i Reference - Submission Author(s)
    ii Reference - Submission Affiliation(s)
  c   Reference - Patents Paten Publication Number
2 a   Epitope Structure Linear Sequences At least one of the three fields from Category # 2 (2a,2b or 2c) has to be filled out.
  b   Epitope Structure SMILES Structure
  c   Epitope Structure Conformational Sequence
3 a   Epitope Structure Epitopic Region / Domain Mandatory field. This Boolean field indicates whether the epitope that is captured is a minimal epitope or contained within a region / domain.
4 a   Epitope Source Epitope Source Nature At least one of the seven fields from Category # 4 (4a, 4b, 4c, 4d, 4e, 4f or 4g) has to be filled out. If the value of natural Antigen, which is a Boolean field, is ’no’, all other Epitope-Source fields are ignored.
  b   Epitope Source Source Species
  c   Epitope Source Gene Name
  d   Epitope Source Protein Name
  e   Epitope Source GenBank ID
  f   Epitope Source Swiss Prot ID
  g   Epitope Source PDB ID
5 a i MHC Binding MHC Allele At least one set of fields from Category # 5 (5a, 5b, 5c, 5d) has to be filled out. All the fields in a subsection has to be filled out if that subsection is selected. For example, if 5a is chosen, all three fields (5a-i,ii,iii) have to be filled out. The following fields - Assay Type, and Qualitative Measurement, can be entered as "Unknown" if the data is unavailable. It’s anticipated that most the data imports from other existing databases might not have the assay related fields
    ii MHC Binding Assay Type
    iii MHC Binding Qualitative Measurement
  b i MHC Ligand Elution MHC Allele
    ii MHC Ligand Elution Assay Type
    iii MHC Ligand Elution Qualitative Measurement
  c i T Cell Response - Assay MHC Allele
    ii T Cell Response - Assay Assay Type
    iii T Cell Response - Assay Qualitative Measurement
  d i B Cell Response - Assay Assay Type
    ii B Cell Response - Assay Qualitative Measurement


Epitope Structure Availability

In the event the exact epitope structure is not given in the reference, follow these guidelines:

I) Contact the corresponding author(s) using the template contact letter provided in the Curation Folder based upon information given in the manuscript. In the internal Curation Tracking System (CTS):

A) Fill out F2: Status should be "Waiting for author’s response". Enter author’s e-mail address and date of e-mail in Comments section of F2 form.
B) Once author provides structure(s): Complete the curation of the article, including "Provided by author" in the Data Location Field in Epitope Structure.
C) Update F2, adding comments to include by whom and when the information was sent.

II) If an e-mail address is not provided in the article, a reference cited by the manuscript regarding the epitope structure may be used for sequence information. The [Epitope Structure] Data Location Field should state where the information was found as cited reference or author communication.

The following format should be used anytime literature is cited in the IEDB: Sette et al. (2007). Nature 48: 1141-7. [PMID:12345678]

When citing epitope location, “Reference cited” should be used in location field and citation information should be placed in comments. Provide the PMID whenever it can be easily obtained.

III) If doubts persist regarding the epitope structure, the data cannot be included in the database. If the author does not respond within two weeks, the reference will be deemed uncuratable. Curation status in Form F2 should be selected as <Uncuratable: Reference Scan> with comments including the reason(s) why the epitope/reference was deemed uncuratable.


Important Note: Cited References The same guidelines are to be applied when researching context information such as the generation of T cell clones or monoclonal antibodies. When researching clone production and mAb generation, only go to references cited by the paper that you are curating. If those references do not provide the needed information, do not continue to search further. Add an immunization comment stating that the details were not provided and clarify this point to the reviewer on the cover sheet, letting the reviewer know that you did look at the references, but still could not find the needed information.