Strong TCR conservation and altered T cell cross-reactivity characterize a B*57-restricted immune response in HIV-1 infection
Strong TCR conservation and altered T cell cross-reactivity characterize a B*57-restricted immune response in HIV-1 infection
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DOI：
10.4049/jimmunol.177.6.3893
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发表时间：
2006-09-15
影响因子：
4.4
通讯作者：
Rowland-Jones, Sarah L.
中科院分区：
文献类型：
--
作者：
Gillespie, Geraldine M. A.;Stewart-Jones, Guillaume;Rowland-Jones, Sarah L.
HLA-B*57与艾滋病的缓慢疾病进展有关，而CD 8（+）T细胞对B*57限制性表位的应答被认为有助于这种保护作用。在这项研究中，我们评估了B*57限制性p24 KAFSPEVIPMF（KF 11）免疫应答，该免疫应答在慢性感染期间是免疫显性的。之前，我们观察到KF 11进化枝变体KGFNPEVIPMF [A2 G，S4 N]和KAFNPEIIMPF [S4 N，V71]共享位置4突变，被KF 11特异性T细胞差异识别。通过结合结构和细胞研究，我们现在证明，尽管单个B*57-肽复合物之间的结构差异很小，但KF 11和[A2 G，S4 N]表位分别在[A2 G，S4 N]和KF 11特异性T细胞中诱导不同的功能应答。最近，我们还阐明了与B*5703复合的KF 11的高度独特的结构，并且现在已经表征了识别该表位的CD 8（+）T细胞库。我们现在报告TCR保守性的显著特征，包括TCR V α和V β链的使用，以及整个高变区。总的来说，我们的研究结果突出了B*5701/B*5703-KF 11特异性免疫应答的不寻常特征，这些特征可能影响疾病进展，并且在设计未来的疫苗方案时可能需要考虑。
HLA-B*57 is associated with slower disease progression to AIDS, and CD8(+) T cell responses to B*57-restricted epitopes are thought to contribute to this protective effect. In this study, we evaluate the B*57-restricted p24 KAFSPEVIPMF (KF11) immune response which is immunodominant during chronic infection. Previously, we observed that the KF11 clade variants KGFNPEVIPMF [A2G,S4N] and KAFNPEIIMPF [S4N,V71], sharing a position 4 mutation, are differentially recognized by KF11-specific T cells. By combining structural and cellular studies, we now demonstrate that the KF11 and [A2G,S4N] epitopes induce distinct functional responses in [A2G,S4N] and KF11-specific T cells, respectively, despite minimal structural differences between the individual B*57-peptide complexes. Recently, we also elucidated the highly distinct structure of KF11 in complex with B*5703, and have now characterized the CD8(+) T cell repertoire recognizing this epitope. We now report striking features of TCR conservation both in terms of TCR V alpha and V beta chain usage, and throughout the hypervariable region. Collectively, our findings highlight unusual features of the B*5701/B*5703-KF11-specific immune responses which could influence disease progression and that might be important to consider when designing future vaccine regimens.