A new variant cytotoxic T lymphocyte escape mutation in HLA-B27-positive individuals infected with HIV type 1.
The immune response in HIV-infected individuals who carry HLA-B27 is characterized by an immunodominant cytotoxic T lymphocyte (CTL) response to a conserved epitope corresponding to amino acids 263-272 of HIV-1 p24 gag. The arginine at position 264 is a crucial anchor residue. Amino acid substitution at 264 from arginine (R) to glycine (G), lysine (K), or threonine (T) results in a low affinity peptide that binds to HLA-B27 inefficiently and is poorly recognized by T cells that respond to the wild-type peptide. These mutants have been characterized as CTL escape mutations. We studied the plasma virus of 20 HLA-B27 longterm nonprogressors: 14 were wild type and 6 were found to be mutant. Five of these carried known escape mutations coding for K or G at position 264. One patient demonstrated a previously undescribed R264Q mutation in 30/31 clones. This altered epitope failed to elicit an IFN-gamma response from PBMC isolated from any of four HLA-B27-positive individuals with strong responses to wild-type peptide. A peptide binding assay confirmed that the R264Q mutant peptide had 30-fold lower binding affinity to HLA-B27 compared to wild type. Therefore, the R264Q variant is a likely novel escape mutation in HLA-B27-positive individuals.
Ammaranond
Palanee
P
National Centre in HIV Epidemiology and Clinical Research, Sydney, NSW, Australia.
Zaunders
John
J
Satchell
Claudette
C
van Bockel
David
D
Cooper
David A
DA
Kelleher
Anthony D
AD
D000595:Amino Acid Sequence; D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics*; D015796:HLA-B27 Antigen / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D016655:HIV Core Protein p24; D015796:HLA-B27 Antigen; D010455:Peptides