A Molecular Basis for the Control of Preimmune Escape Variants by HIV-Specific CD8⁺ T Cells

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• 作者：Kristin Ladell¹ ; ¹¹ ; Masao Hashimoto² ; ¹¹ ; Maria Candela Iglesias³ ; ¹¹ ; Pascal G. Wilmann⁴ ; ¹¹ ; James E. McLaren¹ ; St&eacute ; phanie Gras⁴ ; Takayuki Chikata² ; Nozomi Kuse² ; Solè ; ne Fastenackels³ ; Emma Gostick¹ ; John S. Bridgeman¹ ; Vanessa Venturi⁵ ; Zaï ; na Aï ; t Arkoub⁶ ; Henri Agut⁶ ; David J. van Bockel⁷ ; Jorge R. Almeida³ ; ⁸ ; Daniel C. Douek⁸ ; Laurence Meyer⁹ ; Alain Venet⁹ ; Masafumi Takiguchi² ; ¹² ; Jamie Rossjohn¹ ; ⁴ ; ¹² ; David A. Price¹ ; ⁸ ; ¹² ; Victor Appay³ ; ¹⁰ ; ¹² ; ^{victor.appay@upmc.fr}
• 刊名：Immunity
• 出版年：2013
• 出版时间：21 March, 2013
• 年：2013
• 卷：38
• 期：3
• 页码：425-436
• 全文大小：2396 K

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Summary

The capacity of the immune system to adapt to rapidly evolving viruses is a primary feature of effective immunity, yet its molecular basis is unclear.?Here, we investigated protective HIV-1-specific CD8⁺ T?cell responses directed against the immunodominant p24 Gag-derived epitope KK10 (KRWIILGLNK_263-272) presented by human leukocyte antigen (HLA)-B^?2705. We found that cross-reactive CD8⁺ T?cell clonotypes were mobilized to counter the rapid emergence of HIV-1 variants that can directly affect T?cell receptor (TCR) recognition. These newly recruited clonotypes expressed TCRs that engaged wild-type and mutant KK10 antigens with similar affinities and almost identical docking modes, thereby accounting for their antiviral efficacy in HLA-B^?2705⁺ individuals. A protective CD8⁺ T?cell repertoire therefore encompasses the capacity to control TCR-accessible mutations, ultimately driving the development of more complex viral escape variants that disrupt antigen presentation.