Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand.
Fine specificity of natural killer T cells against GD3 ganglioside and identification of GM3 as an inhibitory natural killer T-cell ligand.
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自然杀伤 T 细胞对 GD3 神经节苷脂的精细特异性以及 GM3 作为抑制性自然杀伤 T 细胞配体的鉴定。
DOI：
10.1111/j.1365-2567.2007.02760.x
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发表时间：
2008
期刊：
影响因子：
6.4
通讯作者：
Chapman,PaulB
中科院分区：
文献类型：
--
作者：
Park,Jun-Eui;Wu,DiannaY;Prendes,Maria;Lu,SharonX;Ragupathi,Govind;Schrantz,Nicolas;Chapman,PaulB
GD3是一种在黑色素瘤上表达的神经节苷脂，是迄今为止唯一一种可以诱导CD1d限制性自然杀伤T （NKT）细胞反应的肿瘤相关糖脂。我们分析了GD3反应性NKT细胞的精细特异性，发现用GD3免疫可诱导两群GD3反应性NKT细胞。一个群体是CD4+CD8 -，对GD3有特异性；另一个群体是CD4 - CD8 -，并以CD1d限制的方式与GM3交叉反应，但不与GM2， GD2或乳糖神经酰胺交叉反应。这表明与GD3反应的T细胞受体可以识别与至少一种en -乙酰-神经氨酸相连的葡萄糖-半乳糖，但不能容纳末端的n -乙酰-半乳糖。GM2、GM3、GD2或乳糖神经酰胺免疫不诱导NKT细胞应答。负载GM3的抗原呈递细胞（APCs）与负载GD3的APCs共同免疫，以CD1d受限的方式抑制NKT细胞对GD3的反应。这种抑制作用对GM3是特异性的，并且是持续2-4天的局部效应。在体外，装载GM3的apc也抑制了NKT细胞对α -半乳糖神经酰胺的白细胞介素- 4反应，但没有抑制干扰素- γ反应。然而，对传统T细胞的辅助T型2反应没有影响。我们发现这种抑制不是由可溶性因子介导的。我们假设GM3诱导APC发生改变，从而抑制辅助性T型2样NKT细胞反应。
GD3, a ganglioside expressed on melanoma, is the only tumour‐associated glycolipid described to date that can induce a CD1d‐restricted natural killer T (NKT)‐cell response. We analysed the fine specificity of GD3‐reactive NKT cells and discovered that immunization with GD3 induced two populations of GD3‐reactive NKT cells. One population was CD4+CD8−and was specific for GD3; the other population was CD4−CD8−and cross‐reacted with GM3 in a CD1d‐restricted manner, but did not cross‐react with GM2, GD2, or lactosylceramide. This indicated that the T‐cell receptors reacting with GD3 recognize glucose‐galactose linked to at least oneN‐acetyl‐neuraminic acid but will not accommodate a terminalN‐acetylgalactosamine. Immunization with GM2, GM3, GD2, or lactosylceramide did not induce an NKT‐cell response. Coimmunization of GM3‐loaded antigen‐presenting cells (APCs) with GD3‐loaded APCs suppressed the NKT‐cell response to GD3 in a CD1d‐restricted manner. This suppressive effect was specific for GM3 and was a local effect lasting 2–4 days.In vitro, GM3‐loaded APCs also suppressed the interleukin‐4 response, but not the interferon‐γ response, of NKT cells to α‐galactosylceramide. However, there was no effect on the T helper type 2 responses of conventional T cells. We found that this suppression was not mediated by soluble factors. We hypothesize that GM3 induces changes to the APC that lead to suppression of T helper type 2‐like NKT‐cell responses.