埃利斯波特
表位
人类白细胞抗原
人类免疫缺陷病毒(HIV)
CD8型
病毒学
生物
免疫学
HLA-A
细胞毒性T细胞
抗原
分子生物学
遗传学
体外
作者
Samantha J Westrop,Nathali Grageda,Nesrina Imami
标识
DOI:10.1016/j.jim.2008.11.003
摘要
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.
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