HPV T cell antigen Database -- FAQ

Questions

1. How many antigens are there in HPVDB?
2. How were T cell epitopes and HLA ligands defined in HPVDB? How many of them are there in HPVdb?
3. How do I get information on an HPV antigen of my interest?
4. How to search for T cell epitopes or HLA ligands?
5. I have an antigen sequence with unknown functions. How do I get more information on this sequence?
6. How do I get a global view of all the experimentally validated T cell epitopes and HLA ligands in an antigen sequence?
7. How do I get a global view of all the experimentally validated T cell epitopes and HLA ligands in all the variants of an antigen of a virus genotype?
8. How do I view all the experimentally validated T cell epitopes and HLA ligands in an antigen sequence and get information on their restricted HLA alleles at the same time?
9. How do I compare multiple sequence variants of a HPV protein?
10. How do I perform detailed sequence variability analysis of a HPV protein?
11. What information does an antigen entry table provide?
12. What information does a T cell epitope/HLA ligand entry table provide?

Answers

1. HPVdb contains 2781 curated antigen entries of antigenic proteins encoded from HPV genome. sequences. Among the 2781 antigen sequences, 1844 are complete sequences and 937 fragment sequences; 162 entries were reviewed by UniPort experts and 2619 entries are unreviewed. These proteins were derived form 18 genotypes of high risk HPV for cancer and 18 genotypes of low risk HPV for cancer. See classification page for details.
   
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2. In building HPV DB, the criterion for antigenic selection of HPV T cell antigens is that antigens must either be presented by one or more HLA alleles or be recognized by T cells through experimental validation. If a peptide had the ability to stimulate T cell function, it was called "T cell epitope". If a peptide only had binding affinity measured or was directly eluted and analyzed by mass spectrometry without activation of T cells, this peptide was called "HLA ligand". These peptides can also be functionally sub-classified in to (a) peptides defined in healthy donors, (b) peptides associated with virus clearance, (c) peptides defined in Cervical Intraepithelial Neoplasia (CIN) and cervical cancer patients, and (d) peptides defined by affinity measurements to HLA (HLA ligands). There are 191 T cell epitopes and 45 HLA ligands in HPVdb.
   
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3. To get information on antigens of your interest, in the menu bar on top of the webpage, select "Record search" in the drop down menu of "Search". If nothing was input into the text box, the search result page will show all the antigens in the database. The search can be refined by selecting protein name, virus genotype, sequence type, and UniProt status from the drop down menus. In the below example figure, the user input antigen name is "HPV16".
   
   

   The search results are displayed into table as shown in below figure. Click on an accession number to go to an antigen entry table for detailed information.
   
   
   
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4. To get information on T cell epitopes or HLA ligands, in the menu bar on top of the webpage, select "Epitope search" in the drop down menu of "Search", and input either an epitope/ligand sequence or an HLA allele of your interest in the text box. If nothing was input into the text box, the search result page will show all the T cell epitopes and HLA ligands in the database. In below example figure, the user input "A*2402".
   
   

   The search results are displayed into table as shown in below figure.
   
   
   
   Click on an accession number in the search result table to go to an epitope or ligand table for detailed information.
   
   
   
   Click on "Check conservation of T cell epitope/HLA ligand" button to see how conserved the epitope/ligand is.
   
   
   
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5. If you have an amino acid sequence and would like to get more information on it, in the menu bar on top of the webpage, select "Blast" in the drop down menu of "Search", to search for similar antigen sequences in HPVdb.
   
   

   On the BLAST result page, you can also select several antigen sequences of your interest and align them with your input sequence.
   
   
   
   
   
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6. In the menu bar on top of the webpage, select View Epitope in the drop down menu of "Tools", select "Format 1", and select an antigen name and HPV genotype in the selection box. Below result page shows all the epitope and ligands highlighted in HPV type 18 E7 sequences.
   
   
   
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7. In the menu bar on top of the webpage, select View Epitope in the drop down menu of "Tools", select "Format 2", and select an antigen name and a HPV genotype in the selection box. Below result page shows the multiple sequence alignment of HPV type 18 E7 sequences with the epitope and ligands highlighted.
   
   
   
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8. In the menu bar on top of the webpage, select View Epitope in the drop down menu of "Tools", select "Format 3", and select an antigen name and a HPV genotype in the selection box. Below result page shows the sequences of HPV type 18 E7 with all the epitope/ligands and their restricted HLA alleles listed below the sequences.
   
   
   
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9. In the menu bar on top of the webpage, select "Alignment" in the drop down menu of "Tools", select a protein, one or more virus genotypes, and a sequence type in the selection box. Below result page shows the multiple sequence alignment of complete HPV type 18 E7 sequences.
   
   
   
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10. In the menu bar on top of the webpage, select "variability analysis" in the drop down menu of "Tools", select a protein, one or more virus genotypes, and a sequence type in the selection box. Below result page shows the multiple sequence alignment of complete HPV type 16 E7 sequences.
    
    
    
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11. An antigen record table provides below information:

    HPVACC	Unique accession number for an antigen record in HPVdb
    Date	Entry date of the record
    Last updated date	Latest date of information update on the entry
    Antigen Name	Protein name
    Full Name	Complete protein names from Uniprot
    Virus genotype	Classification of HPV genotype according to International Committee on Taxonomy of Viruses (ICTV)
    UniProt ID	Cross-references to corresponding record in Uniprot database
    UniProt status	reviewed or unreviewed
    Sequence status	complete or fragment
    T cell epitope	Epitope sequence	Position	HLA allele	Reference
    	T cell epitope sequence	Position of the epitope in the antigen sequence	restricted HLA allele	PubMed link of the paper containing the T cell epitope validation result
    HLA ligand	Ligand Sequence	Position	HLA allele	Reference
    	HLA ligand sequence	Position of the ligand in the antigen sequence	restricted HLA allele	PubMed link of the paper containing the HLA ligand binding result
    Predicted HLA binders	Prediction of 9-mer peptide binding affinities to 15 HLA Class I and Class II alleles, A*0101, A*0201, A*0301, A*1101, A*2402, B*0702, B*0801, B*1501, DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501.
    Antigen sequence	Protein sequence of the antigen

    
    
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12. A T cell epitope/HLA ligand table provides below information:

    TACC or LACC	Unique accession number for a T cell epitope or HLA ligand in HPVdb
    Epitope or Ligand sequence	the peptide sequence
    HLA allele	The restricted HLA allele
    Reference	PubMed ID(s) hyperlinked to the corresponding PubMed abstract page(s)
    IEDB ID	Cross-references to IEDB database if the information is available

    
    Below the table, there is a multiple sequence alignment of all sequences containing the epitope/ligand.
    
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