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Disclaimer

The funding for the HCV database project has stopped, and this website and the HCV immunology database are no longer maintained. The site will stay up, but problems will not be fixed. The database was last updated in September 2007. The HIV immunology website contains the same tools, and may be usable for non-HCV-specific analyses. For new epitope information, users of this database can try the Immuno Epitope Database (http://www.immuneepitope.org). More information is here.

HCV Immunology Search Help

HCV Immunology Search Help

T Cell Epitopes

T cell epitopes are categorized into cytotoxic T lymphocytes (CTL) and helper T lymphocytes (T-helper). The database organization for CTL and T-helper is identical, so they are described together.

Summary

The T cell databases include tables, maps, and associated references of HCV-specific T cell epitopes arranged sequentially according to the location of the proteins in the HCV genome. We attempted to make this section as comprehensive as possible, requiring that the epitope be contained within a defined region of a maximum of 30 amino acids, but not that the optimal boundaries be defined. Studies that were based on the analysis of whole proteins are described at the end of each protein section. The same epitope can have multiple entries, and each entry represents a single publication in this section of the database. T cell protein reactions with no well-defined epitopes are listed at the end of each protein section.

Recent studies utilize multiple functions attributed to T cells to define responses, and the simple distinctions of cytotoxic T-cell and helper T-cells have become blurred as more is learned about the range of responses triggered in CD4 and CD8 positive T-cells responding to antigenic stimulus. When adding the most recent studies, we have tried to place T cell responses in a reasonable manner into our traditional helper T cell and CTL sections, and to specify the assay used to measure the response in each study.

T cell epitopes are arranged by protein position. The table entries are sorted in a nested way---first by protein, then by H77 start location within the protein, then by H77 end location and finally by HLA presenting molecule. Epitopes for which the H77 location is unknown appear at the end of the listing of the protein in which they are located.

T Cell Epitope Tables

Each T cell epitope has a multi-part basic entry:

Record number A unique number assigned by the database, in approximate order of entry. Please refer to this number if you have any comments or questions about an entry.

HCV protein The protein for which the epitope was defined.

 

H77 location The viral strain H77 (GenBank Accession Number M67463) is used as a reference strain throughout the database. The position of the defined epitope location relative to the sequence of the H77 protein is indicated. The numbering in this table corresponds to the protein maps. Because of HCV variation the epitope may not always be present in H77, the position in H77 indicates the position aligned to the epitope. The precise positions of an epitope on the H77 reference strain can be readily obtained using the Sequence Locator Tool.

Author location The amino acid positions of the epitope boundaries and the reference sequence are listed as given in the primary publication. If the strain name, accession number or genotype of the reference sequence were noted in the primary publication, they are displayed here as well.

Epitope  The amino acid sequence of the epitope of interest as defined in the reference, based on the reference strain used in the study defining the epitope. If only the position numbers and not the actual peptide sequence were specified in the original publication, we tried to fill in the peptide sequence based on the position numbers and reference strain. If the sequences were numbered inaccurately by the primary authors, or if we made a mistake in this process, we may have misrepresented the binding site's amino acid sequence. Because of this uncertainty, epitopes that were not explicitly listed in the primary publication are followed by a question mark in the table.

Epitope name The epitope name (if available) as it was given in the primary publication.

Species and MHC/HLA: Information about the species that the T-cell response is being studied in (human, chimpanzee, mouse) and about the presenting MHC or HLA molecule, as described in the primary publication (for example, human (A*0201)).    

Immunogen The antigenic stimulus that generated the initial CTL response, for example, HCV infection or vaccine. If a vaccine stimulated the response, additional search fields are available that describe the vaccine.

 

Vaccine details  Data included only if the immunogen was a vaccine.

 

Vaccine type The vaccine construct and boost.

 

Vaccine strain The strain of HCV used for the antigen.

 

Vaccine component The HCV protein (complete or partial) included in the vaccine.

 

Adjuvant Traditional stimulatory agent sometimes included in a vaccine formulation to enhance or modify the immune-stimulating properties of a vaccine.

Keywords Searchable classes of HCV immunological studies of interest.

Experimental methods  Assays used to measure the T cell response in the study (T cell ELISPOT, Chromium-release assay, Intracellular cytokine staining, Proliferation, etc.).

Author Any author from the primary publication.

Reference The primary reference (sometimes two or more directly related studies are included). Some of the earlier references include notes. On the web site, these references are linked to PubMed.

Notes A brief description of what was learned about the T-cell response from the study. Examples of kinds of things included in the notes would be: correlation with survival in longitudinal studies, immune escape, quantitative features of the response, HCV genotype cross-reactivity, etc.

 

HCV Protein Epitope Maps

All HCV T cell epitopes mapped to within a region of 21 amino acids or less are indicated on the HCV protein epitope maps. The location and HLA restriction elements of CTL epitopes are indicated on protein sequences of H77. These maps are meant to provide the relative location of defined epitopes on a given protein, but the H77 sequence may not actually carry the epitope of interest, as it may vary relative to the sequence for which the epitope was defined. Epitopes with identical boundaries and HLA fields are included in the maps only once. If one laboratory determines HLA presenting molecules at the serotype level (example: A2) and another at the genotype level (example: A*0201) both will be included in the map. MHC specificities are indicative of the host species; when no MHC presenting molecule is defined, the host species is noted.

Alignments

Epitope alignments can be generated using the epitope search tools. All epitopes are aligned to the H77 sequence, with the sequence used to define the epitope indicated directly above it. Sequences are sorted by their genotype and country of origin.

The master alignment files from which the epitope alignments were created are available at our ALIGNMENTS site. A dash indicates identity to the consensus sequence, and a period indicates an insertion made to maintain the alignment. Stop codons are indicated with a $, and frameshifts by a #, or ambiguous codons (nucleotide was r, y, or n) by an x; they are inserted to maintain the alignments. In consensus sequences an upper case letter indicates the amino acid was present in all sequences, a lower case letter indicates the amino acid was present in most sequences in a given position, and a question mark indicates two or more amino acids were represented with equal frequency.

T cell Epitope Summary Tables

This is a list of all HCV T cell epitopes mapped to within a region of 21 amino acids or less. The protein, H77 location, host species and HLA restriction elements of T cell epitopes are provided. Identical entries are shown only once. The epitope sequence is a link to the database (CTL or Helper), which will provide details of all epitopes containing that sequence.

 

HCV Antibody Binding Sites

Summary

The antibody database summarizes HCV-specific antibodies (Abs) arranged sequentially according to the location of their binding domain, organized by protein. We attempted to make this section as comprehensive as possible. For the monoclonal antibodies (MAbs) capable of binding to linear peptides, we require that the binding site be contained within a region of 30 or so amino acids to define the epitope, but not that the precise boundaries be defined. Currently the database contains mainly studies of monoclonal Abs, but some studies of polyclonal Ab responses are also included and we are adding more. Responses that are just characterized by binding to a protein, with no known specific binding site, are also listed.

Antibody Tables

Each MAb or polyclonal response has a multi-part basic entry and several search fields.This is a description of the database fields in the search and results pages:

Record number A unique number assigned by the database, in approximate order of entry. Please refer to this number if you have any comments or questions about an entry.

MAb ID The name of the monoclonal antibody with synonyms in parentheses. MAbs sometimes have several names. For example, punctuation can be lost and names are shortened. Polyclonal responses are listed as "polyclonal" in this field.

HCV protein The protein for which the epitope was defined.

H77 location The viral strain H77 (GenBank Accession Number M67463) is used as a reference strain throughout the database. The position of the defined epitope location relative to the sequence of the H77 protein is indicated. The numbering in this table corresponds to the protein maps. Because of HCV variation the epitope may not always be present in H77, the position in H77 indicates the position aligned to the epitope. The precise positions of an epitope on the H77 reference strain can be readily obtained using the Sequence Locator Tool.

Author location The amino acid positions of the epitope boundaries and the reference sequence are listed as given in the primary publication. If the strain name, accession number or genotype of the reference sequence were noted in the primary publication, they are displayed here as well.

Epitope The amino acid sequence of the binding region of interest, based on the reference strain used in the study defining the binding site. On occasions when only the position numbers and not the actual peptide sequence was specified in the original publication, we tried to fill in the peptide sequence based on the position numbers and reference strain. If the sequences were numbered inaccurately by the primary authors, or if we made a mistake in this process, we may have misrepresented the binding site's amino acid sequence. Because of this uncertainty, epitopes that were not explicitly written in the primary publication, that we determined by looking up the reference strain and the numbered location, are followed by a question mark in the table.

Epitope name The epitope name (if available) as it was given in the primary publication.

Immunogen The antigenic stimulus of the original B cell response. Often this is an HCV infection. If a vaccine was used as the original antigenic stimulation, not a natural infection, this is noted on a separate line, and additional information about the vaccine antigen is provided as available.

Vaccine details Data included only if the immunogen was a vaccine.

Vaccine type The vaccine construct and boost.

Vaccine strain The strain of HCV used for the antigen.

Vaccine component The HCV protein (complete or partial) included in the vaccine.

Adjuvant Traditional stimulatory agent sometimes included in a vaccine formulation to enhance or modify the immune-stimulating properties of a vaccine.

Neutralizing yes or no. Neutralizing properties of the antibody---often different studies involving the same antibody will report this differently, so this classification is somewhat subjective. No information in this field means that neutralization was either not discussed or unresolved in the primary publications referring to the MAb.

Species(Isotype) The host that the antibody was generated in, and the isotype of the antibody.

Ab Type Classes of antibodies have shared properties with regard to their binding site and can be grouped; for example they might bind to a similar region (like Core N-terminus) or near a common functional domain (like the CD81 binding site).

Research Contact Information about an antibody or how to obtain it, as well as to provide credit.

Notes Describe the context of each study, and what was learned about the antibody in the study.

Keywords Searchable classes of HCV immunological studies of interest.

Author Any author from the primary publication.

References All publications that we could find that refer to the use of a specific monoclonal antibody.

HCV Protein Binding Site Maps

The names of MAbs and the location of well characterized linear binding sites of 21 amino acids or less are indicated relative to the protein sequences of the H77 strain. This map is meant to provide the relative location of epitopes on a given protein, but the H77 sequence may not actually bind to the MAb of interest, as it may vary relative to the sequence for which the epitope was defined. Above each linear binding site, the MAb name is given followed by the species in parentheses. Human is represented by h, non-human primate by p, mouse by m, and others by o. More precise species designations for any given MAb can be found using the web search interface.

Search Fields

This is a brief description of the database fields in the search and results pages. Please see above for more details.

HCV protein The protein for which the epitope was defined. When an epitope spans two proteins that we treat separately in the database, such as E1 and E2, both are indicated.

Defined epitope An epitope or reactive peptide with a known protein sequence.

Undefined epitope A reactive peptide or protein for which the binding site is not exactly known. This could either be because it it was unspecified by the authors (i.e. a polyclonal response to E2) or because it is a conformational epitope for an antibody that binds to discontinuous amino acids in the folded protein.

Epitope The amino acid sequence of the epitope or short reactive peptide in which the epitope is embedded.

Immunogen The stimulus of the original immune response under study.

Vaccine details Data included only if the immunogen was a vaccine.

Vaccine type The vaccine construct and boost.

Vaccine strain The strain of HCV used for the vaccine antigen.

Vaccine component The HCV protein (complete or partial) included in the vaccine.

Adjuvant Traditional adjuvants or chemokines.

Species The species in which the immune response was stimulated.

HLA The HLA (or MHC) presenting molecules as described by the primary authors.

Isotype The type of antibody, such as IgG, IgA...

Author Any one author from primary publication.

Keywords Searchable classes of HCV immunological studies of interest.

Experimental methods Methods used by the authors to test the immune response.

Mab ID Name of monoclonal antibody or "polyclonal" if a general response is being studied.

H77 Location Epitope position numbers in the H77 reference strain.

Author Location Epitope location as reported by the authors. Includes strain and subtype from which the epitope was derived.

Epitope Name Epitope name as reported by the authors.

Donor HLA The full HLA type of the infected individual.

Ab Type Classes of antibodies have shared properties with regard to their binding site and can be grouped.

Neutralizing Neutralizing properties of the antibody---often different studies involving the same antibody will report this differently, so this classification is somewhat subjective.

Research Contact The person or lab that generated or provides the antibody.

 
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