HIV molecular immunology database

 

Variants Database Help

Description

The variants database contains information about sequence variants and mutations of HIV-1 CTL epitopes. Only variants tested for immunological response are included. Variants are usually omitted if the paper only provides sequence or statistical data.

For general information about the HIV Immunology databases and searches, see HIV Immunology Search Help.

Variants Search & Results Fields

This is a brief description of the database fields in the variant search and results pages.

HIV protein
The protein for which the epitope was defined. When an epitope spans two proteins that we treat separately in the database, such as p17-p24, both are indicated.
HXB2 location
The HXB2 protein coordinates within the protein selected in the "HIV protein" field above.
Three options determine the type of search:
  1. Results overlap with query location: finds epitopes that overlap any residue of the specified location. To find epitopes that contain a single specific residue, you can enter the same coordinate number in both boxes.
  2. Results contained within query location: finds epitopes that are contained within the specified range. Results will be the same length or shorter than the query.
  3. Results exact match to query location: finds epitopes that have exactly the specified start and stop coordinates.
Epitope or Variant Sequence
The amino acid sequence of the epitope or variant.
Three options determine the type of search:
  1. Results contain query sequence: finds epitopes that contain the query sequence. Results will be the same length or longer than the query.
  2. Results exact match to query sequence: finds epitopes with the exact coordinates and exact sequence as the query.
  3. Results fuzzy match to query sequence: finds epitopes with the exact coordinates as the query, but with up to 25% difference in the amino acid sequence.
Record number
A unique number assigned to an epitope by the database. Please refer to this number if you have any comments or questions about an entry.
Variant record number
A unique number assigned to a variant by the database. Please refer to this number if you have any comments or questions about an entry.
Mutation Type
Mutations are classified into various types, depending on the evidence presented in the paper. Assigning the mutation type is sometimes a subjective judgement of the annotator; it is not always clear in the paper. Read the Notes for the variant carefully, and refer to the original paper if necessary. Abbreviations are defined below.
MHC/HLA
The MHC (or HLA) presenting molecules as described by the primary authors.
Method
The method(s) used to ascertain the type of mutant.
Notes
In the notes for the variant, the annotator explains the evidence for assigning the mutation type.

 

List of Variant and Mutation Types

Code Mutation type Description
? unclear Not clear from the paper, for example "E ?" Or "IE ?"
A HLA association Variant is statistically associated with a particular HLA molecule. Since we focus on experimentally verified epitope variants, the variant with this mutation is entered only if it is already described as an experimentally determined mutation.
CE calculated escape Predicted escape as shown by statistical correlation or other computational methods in a large cohort. Since we focus on experimentally verified epitope variants, the variant with this mutation is entered only if it is already described as an experimentally determined mutation.
CHB calculated diminished HLA binding Predicted decrease in binding to HLA as shown by algorithm(s). Since we focus on experimentally verified epitope variants, the variant with this mutation is entered only if it is already described as an experimentally determined mutation.
CM compensatory mutation Variant is associated with a compensatory mutation. This could be a compensatory mutation outside epitope boundaries, or a mutation within epitope boundaries, compensating for the same epitope or for a variant of another epitope. Each particular entry is explained in the variant note.
DHB diminished HLA binding or increased off-rate Decreased binding (or increased off-rate) to presenting HLA as compared to binding by original epitope.
DI drug induced Treatment with antiretroviral drugs induces this variant.
DR diminished response Experimental data suggests a partial escape by decreased CTL response, but authors do not call it an escape (judgment call of annotator).
E escape documented in this paper Same as NSF (non-susceptible form) but called an escape when dynamic changes seen in a longitudinal or transmission study or when author claims escape.
EL epitope loss Entire sequence of epitope lost in variant virus.
IE inferred escape Variant is predicted to be an escape by longitudinal study or transmission study (but the reactivity of the variant is not tested experimentally).
LE literature escape Escape previously documented in the literature (according to the authors).
NSF non-susceptible form No CTL response when patient cells are challenged with the variant peptide.
NSF-2 non-susceptible form-2 Neither index nor variant peptides are recognized by CTL, but the index peptide is a known epitope and, in most cases, there was a prior patient response to it.
OV observed variant variant sequence observed in longitudinal or transmission study.
P processing Variant escapes CTL detection by altering epitope processing in subcellular organelles, experimentally verified.
R reversion Variant reverts to wild type epitope sequence as documented by sequence, experimental studies or literature.
RCOK replicative capacity is not abrogated Variant does not cause loss of viral replication, as shown by replication assays.
RCR replicative capacity reduced Variant is associated with a reduction or loss (abrogation) of replication of the virus, as shown by replication assays.
SF susceptible form CTL response is elicited when patient cells are challenged with the variant peptide.
SNSF subtype-specific non-susceptible form No CTL response when patient cells are challenged with the variant peptide in the course of subtype comparative studies, however the same epitope from a different subtype does elicit CTL response.
SSF subtype-specific susceptible form CTL response is elicited when patient cells are challenged with the variant peptide in the course of subtype comparative studies, i.e. patient cells can recognize at least two different viral subtype variants.
TCR TCR related mutation Variant does not bind or shows decreased binding to TCR.

 

Codes and Symbols in Variants

Symbol Meaning Example
x Lower case letters indicate a mutation. Variant SLYNTVAvL indicates a mutation from T to V in the epitope SLYNTVATL.
(x) Round brackets in the epitope variant designate an insertion. Variant PLTF(a)GWCYKL has an A inserted between 4F and 5G (Nef 139F and 140G) in the epitope PLTFGWCYKL. Insertion position within the epitope is reported as (4.1)A, and insertion position in the protein is reported as Nef (139.1)A.
'-' Dash in the epitope variant denotes a deletion. Variant RAEQ-SQdV of epitope RAEQASQEV has lost amino acid A at position 5.
{xxx} Curly brackets in the variant are used to designate a flanking region when there is a mutation upstream or downstream of the epitope. Variant {p}ISPRTLNAW of epitope {A}lSPRTLNAW means that there is an A-to-P mutation upstream of the epitope N-terminus.
'+n' Mutation in the downstream epitope flanking region. Variant SPAIFQSSM{TKILd} of the epitope SPAIFQSSM{TKILE} has an E-to-D mutation 5 amino acids downstream of the epitope C-terminus.
'-n' Mutation in the upstream epitope flanking region. Variant {rWEKI}RLRPGGKKK of the epitope {KWEKI}RLRPGGKKK has a K-to-R mutation 5 amino acids upstream of the epitope N-terminus.
'*' A non-mutated amino acid in the epitope flanking region either upstream or downstream of the epitope. Each '*' is one amino acid, and its sequence location is specific. This notation is used when the amino acids between the epitope and the mutation site are not reported in the original publication. Variant KIRLRPGGK{*t} of epitope KIRLRPGGK has an R-to-T processing mutation 2 amino acids downstream. The intervening amino acid was not reported.
'...' An unspecified number of amino acids were present between the mutation position in the flanking region and the epitope. This notation is used when the exact mutation position upstream or downstream is >5 amino acids away, or was not reported in the original publication. In the former case, the mutation position is reported. Variant {q...}TSnLQEQIGW of epitope {H...}TSTLQEQIGW has an unspecified number of non-mutated amino acids between the N-terminus of the epitope and the upstream H-to-Q mutation.

 

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