一图一会：CTL and HIV-1

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Figure legend:
In HIV-infected individuals with HLA class I alleles that are associated with effective control of the virus (such as HLA-B57 and HLA-B27), Gag-specific responses are generated in acute infection. Wild-type virus-specific-cytotoxic T lymphocytes (CTLs) recognize virus-infected cells early in the viral life cycle, before Nef-mediated MHC class I downregulation. Escape mutations that are typically selected in Gag reduce in vitro viral fitness. Remaining wild-type virus-specific CTL responses can contain the infection until new escape variants are selected. However, increasing numbers of costly escape mutations further limit the replicative capacity of the virus, thereby facilitating effective killing of virus-infected cells by remaining CTLs. TCR, T-cell receptor.

图片出处：

Impact of MHC class I diversity on immune control of immunodeficiency virus replication

Philip J. R. Goulder & David I. Watkins

Nature Reviews Immunology 8, 619-630 (August 2008)

doi:10.1038/nri2357

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关于HIV病毒的逃逸和CTL的穷追不舍的故事在HLA-B27和病毒KK10 抗原的研究上展开了这么一场特俗的博弈。请看图：

(a) Highly biased public TCRs targeting the HLA-B27 restricted immunodominant epitope Gag, amino acid residues 263–272 (KK10).
(b) The dominant Vβ clonotype frequencies might be maintained in parallel with mutations that show little compromise on replicative fitness.
(c) Mutations in MHC class I anchor residues lead to loss of binding and clonal extinction.
(d) Highly diverse private TCR Vβ usage might also reflect an immunodominant response in which a spectrum of avidities and killing thresholds exist.

参考阅读：
1.Lessons learned from natural infection: focusing on the design of protective T cell vaccines for HIV/AIDS  PMID: 20089450
2.A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8+ T Cells              PMID: 23521884

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