Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens.
Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens.
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DOI：
10.1038/ncomms10570
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发表时间：
2016-02-15
影响因子：
16.6
通讯作者：
Uldrich AP
中科院分区：
文献类型：
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作者：
Le Nours J;Praveena T;Pellicci DG;Gherardin NA;Ross FJ;Lim RT;Besra GS;Keshipeddy S;Richardson SK;Howell AR;Gras S;Godfrey DI;Rossjohn J;Uldrich AP
自然杀伤T（NKT）细胞功能的关键是其T细胞受体（TCR）和CD 1d-抗原复合物之间的相互作用。然而，NKT细胞库的多样性以及随后与CD 1d抗原的相互作用仍不清楚。我们描述了一种非典型的CD 1d-α-半乳糖神经酰胺（α-GalCer）反应性人NKT细胞群体，其与原型TRAV 10-TRAJ 18-TRBV 25 -1+ I型NKT细胞库明显不同。这些细胞表达一系列TCR α链和β链，显示出对糖脂抗原的差异识别。两种非典型NKT TCR（TRAV 21-TRAJ 8-TRBV 7 -8和TRAV 12 -3-TRAJ 27-TRBV 6 -5）与CD 1d的A′-口袋正交结合，采用不同的对接模式，与所有I型NKT TCR-CD 1d-抗原复合物的对接模式形成对比。此外，与α-GalCer的相互作用在I型和这些非典型NKT TCR之间不同。因此，不同的NKT TCR库使用表现为不同的对接策略和对CD 1d-α-GalCer和相关抗原的特异性，从而为不同的糖脂抗原识别提供了更大的范围。 I型NKT细胞的不变αβTCR识别由CD 1d呈递的脂质α-GalCer。在本文中，作者描述了具有不同TCR的非典型α-GalCer反应性NKT细胞，其以不同于I型NKT细胞的方式与CD 1d-α-GalCer结合，从而揭示了脂质抗原识别的更大多样性。
Crucial to Natural Killer T (NKT) cell function is the interaction between their T-cell receptor (TCR) and CD1d-antigen complex. However, the diversity of the NKT cell repertoire and the ensuing interactions with CD1d-antigen remain unclear. We describe an atypical population of CD1d–α-galactosylceramide (α-GalCer)-reactive human NKT cells that differ markedly from the prototypical TRAV10-TRAJ18-TRBV25-1+ type I NKT cell repertoire. These cells express a range of TCR α- and β-chains that show differential recognition of glycolipid antigens. Two atypical NKT TCRs (TRAV21-TRAJ8-TRBV7–8 and TRAV12-3-TRAJ27-TRBV6-5) bind orthogonally over the A′-pocket of CD1d, adopting distinct docking modes that contrast with the docking mode of all type I NKT TCR-CD1d-antigen complexes. Moreover, the interactions with α-GalCer differ between the type I and these atypical NKT TCRs. Accordingly, diverse NKT TCR repertoire usage manifests in varied docking strategies and specificities towards CD1d–α-GalCer and related antigens, thus providing far greater scope for diverse glycolipid antigen recognition. The invariant αβTCR of type I NKT cells recognizes a lipid α-GalCer presented by CD1d. Here the authors describe atypical α-GalCer-reactive NKT cells with diverse TCRs, which bind to CD1d-α-GalCer in a manner distinct from type I NKT cells, thus unveiling greater diversity in lipid antigen recognition.