Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E.
Broadly targeted CD8⁺ T cell responses restricted by major histocompatibility complex E.
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DOI：
10.1126/science.aac9475
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发表时间：
2016-02-12
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影响因子：
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通讯作者：
Picker LJ
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作者：
Hansen SG;Wu HL;Burwitz BJ;Hughes CM;Hammond KB;Ventura AB;Reed JS;Gilbride RM;Ainslie E;Morrow DW;Ford JC;Selseth AN;Pathak R;Malouli D;Legasse AW;Axthelm MK;Nelson JA;Gillespie GM;Walters LC;Brackenridge S;Sharpe HR;López CA;Früh K;Korber BT;McMichael AJ;Gnanakaran S;Sacha JB;Picker LJ
主要组织相容性复合体（MHC）-E是一种高度保守、广泛表达的非经典MHC-Ib分子，具有有限的多态性，主要参与NK细胞调节。我们发现，用ΔRh157.5/.4恒河猴巨细胞病毒（RhCMV）载体接种恒河猴（RM）导致高度变化的肽表位向CD 8 α/β+ T细胞的MHC-E限制性呈递，在所有测试的抗原中，每100个氨基酸约有4个不同的表位。计算结构分析表明，MHC-E提供了一个稳定的，开放的结合槽内的不同侧链相互作用的异质性化学环境。由于MHC-E在感染HIV/SIV和其他持久性病毒的细胞上上调以逃避NK细胞活性，因此MHC-E限制性CD 8 + T细胞应答具有利用病原体免疫逃避适应的潜力，这种能力可能赋予这些非常规应答上级功效。
Major histocompatibility complex (MHC)-E is a highly conserved, ubiquitously expressed, non-classical MHC-Ib molecule with limited polymorphism primarily involved in NK cell regulation. We found that vaccination of rhesus macaques (RM) with ΔRh157.5/.4 Rhesus Cytomegalovirus (RhCMV) vectors results in MHC-E-restricted presentation of highly varied peptide epitopes to CD8α/β+ T cells, approximately 4 distinct epitopes per 100 amino acids in all tested antigens. Computational structural analysis revealed that MHC-E provides heterogeneous chemical environments for diverse side chain interactions within a stable, open binding groove. Since MHC-E is up-regulated on cells infected with HIV/SIV and other persistent viruses to evade NK cell activity, MHC-E-restricted CD8+ T cell responses have the potential to exploit pathogen immune evasion adaptations, a capability that might endow these unconventional responses with superior efficacy.