Major histocompatibility complex class I-restricted alloreactive CD4+ T cells

Major histocompatibility complex class I-restricted alloreactive CD4+ T cells
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DOI:
10.1111/j.1365-2567.2004.01857.x
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发表时间:
2004-05-01
期刊:
影响因子:
6.4
通讯作者:
Gaston, JSH
Gaston, JSH
中科院分区:
医学2区
文献类型:
--
作者:
Boyle, LH;Goodall, JC;Gaston, JSH

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尽管已明确CD4(+) T细胞通常识别主要组织相容性复合体(MHC) II类分子,但偶尔也有报道MHC I类反应性CD4(+) T细胞。在这里,我们描述了六种 MHC I 类反应性 CD4(+) T 细胞系的分离和表征,这些细胞系是通过将 CD4(+) 外周血 T 细胞与 MHC II 类阴性、与抗原加工相关的转运蛋白 (TAP) 阴性细胞系 T2 共培养而获得的,并转染了人类白细胞抗原 (HLA)-B27。 MHC I 类特异性单克隆抗体 (mAb) W6/32 抑制反应,证明了 MHC I 类分子的直接识别。在四种情况下,限制性元件被明确鉴定为 HLA-A2,因为这些克隆的反应被 MA2.1(一种 HLA-A2 特异性单克隆抗体)完全抑制。有趣的是,三种CD4(+) T细胞系仅对表达HLA-B27的细胞作出反应,无论其限制性等位基因如何,这表明HLA-B27可能是由刺激性MHC I类等位基因呈递的肽的来源。此外,这些CD4(+) MHC I类同种反应性T细胞系可以识别TAP缺陷细胞,因此可能与TAP分子表达降低的情况(例如病毒感染和细胞转化)具有特殊的临床相关性。
Although it is well established that CD4(+) T cells generally recognize major histocompatibility complex (MHC) class II molecules, MHC class l-reactive CD4(+) T cells have occasionally been reported. Here we describe the isolation and characterization of six MHC class I-reactive CD4(+) T-cell lines, obtained by co-culture of CD4(+) peripheral blood T cells with the MHC class II-negative, transporter associated with antigen processing (TAP)-negative cell line, T2, transfected with human leucocyte antigen (HLA)-B27. Responses were inhibited by the MHC class I-specific monoclonal antibody (mAb), W6/32, demonstrating the direct recognition of MHC class I molecules. In four cases, the restriction element was positively identified as HLA-A2, as responses by these clones were completely inhibited by MA2.1, an HLA-A2-specific mAb. Interestingly, three of the CD4(+) T-cell lines only responded to cells expressing HLA-B27, irrespective of their restricting allele, implicating HLA-B27 as a possible source of peptides presented by the stimulatory MHC class I alleles. In addition, these CD4(+) MHC class I alloreactive T-cell lines could recognize TAP-deficient cells and therefore may have particular clinical relevance to situations where the expression of TAP molecules is decreased, such as viral infection and transformation of cells.