Novel approach to recognition of predicted HIV-1 Gag B3501-restricted CD8 T-cell epitopes by HLA-B3501(+) patients: confirmation by quantitative ELISpot analyses and characterisation using multimers.
Exploring the intricacies of CD8(+) T-cell epitope recognition using emerging technologies to combine assessment of affinity, phenotype and resulting polyfunctional efficacy advances our understanding of HIV-1 immunopathogenesis and disease progression. Complexities within T-cell antigen recognition, such as epitope:MHC binding, stability and affinity, appear to influence the distinction between protective and ineffective anti-HIV-1 immune responses, which are thought to govern rate of disease progression. This study utilises the novel ProImmune REVEAL and ProVE(R) technology of rapid peptide synthesis, binding and affinity assays, and pentamer synthesis in conjunction with flow cytometry and simultaneous assessment of multiple CD8(+) T-cell effector functions in response to HLA-B3501-restricted HIV-1 Gag peptides, to discover new T-cell epitopes. The predicted HLA-B3501-restricted peptides, HPVHAGPIA and YPLTSLRSL, and relevant pentamers were used in parallel to validate T-cell epitopes on clinical HIV-1(+) samples, confirming correlation between the expected superior immunogenicity of newly discovered epitopes and the ex vivo T-cell response. Such a platform should be employed in prophylactic and therapeutic vaccine settings.
Westrop
Samantha J
SJ
Department of Immunology, Imperial College London, Chelsea and Westminster Hospital, 369, Fulham Road, London SW10 9NH, United Kingdom.
Grageda
Nathali
N
Imami
Nesrina
N
D016915:AIDS Vaccines / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping / Q000379:methods*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D015797:HLA-B35 Antigen; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008297:Male; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015235:HLA-B Antigens; C500431:HLA-B*35:01 antigen; D015797:HLA-B35 Antigen; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D054301:gag Gene Products, Human Immunodeficiency Virus