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克隆性T淋巴细胞对HLA - A2分子精细结构的识别。

Clonal T lymphocyte recognition of the fine structure of the HLA-A2 molecule.

作者信息

Brenner M B, McLean J, Yang S Y, van der Poel J J, Pious D, Strominger J L

出版信息

J Immunol. 1985 Jul;135(1):384-90.

PMID:2582041
Abstract

A human alloimmune cytotoxic T lymphocyte (CTL) clone (4E4) was generated against the HLA-A2 molecule. Lysis of 51Cr-labeled HLA-A2 target cells was blocked by monoclonal antibodies (mAb), including mAb PA2.1 (anti-HLA-A2), mAb BB7.2 (anti-HLA-A2), mAb 4B (anti-HLA-A2-plus-A28), mAb MA2.1 (anti-HLA-A2-plus-B17), and mAb W6/32 (anti-HLA-A,B,C), which are directed against different serologic epitopes on the HLA-A2 molecule. However, HLA-A2 mutant lines lacking the serologic epitope recognized by mAb BB7.2 (anti-HLA-A2) were efficiently lysed by CTL 4E4. Thus, although mAb may block cytolysis, the HLA-A2 epitope recognized the 4E4 CTL clone is distinct from the HLA-A2-specific epitope recognized by serologic reagents. Moreover, analysis of HLA-A2 population variants revealed that only the predominant HLA-A2.1 subtype molecule was recognized by CTL 4E4. No cross-reactivity on other, biochemically related HLA-A2 population subtypes was observed, including HLA-A2.2 cells (Hill, CVE, ZYL, M7), HLA-A2.3 cells (TENJ, DK1), or HLA-A2.4 cells (CLA, KNE). This CTL clone appears to recognize a single epitope and, like monoclonal antibody counterparts, can be used to discriminate among immunogenic cellular and serologic epitopes on closely related HLA-A2 molecules. On the basis of the known sequence changes in mutant and subtype HLA-A2 molecules, it appears that the sequence spanning residues 147 to 157 may be critical for cellular recognition of this Class I MHC molecule.

摘要

产生了一种针对HLA - A2分子的人同种异体免疫细胞毒性T淋巴细胞(CTL)克隆(4E4)。用单克隆抗体(mAb)阻断了51Cr标记的HLA - A2靶细胞的裂解,这些单克隆抗体包括mAb PA2.1(抗HLA - A2)、mAb BB7.2(抗HLA - A2)、mAb 4B(抗HLA - A2加A28)、mAb MA2.1(抗HLA - A2加B17)和mAb W6/32(抗HLA - A、B、C),它们针对HLA - A2分子上不同的血清学表位。然而,缺乏mAb BB7.2(抗HLA - A2)所识别的血清学表位的HLA - A2突变株系被CTL 4E4有效裂解。因此,尽管单克隆抗体可能阻断细胞溶解,但4E4 CTL克隆所识别的HLA - A2表位与血清学试剂所识别的HLA - A2特异性表位不同。此外,对HLA - A2群体变体的分析表明,只有主要的HLA - A2.1亚型分子被CTL 4E4识别。未观察到对其他生化相关的HLA - A2群体亚型有交叉反应,包括HLA - A2.2细胞(Hill、CVE、ZYL、M7)、HLA - A2.3细胞(TENJ、DK1)或HLA - A2.4细胞(CLA、KNE)。该CTL克隆似乎识别单一表位,并且与单克隆抗体类似物一样,可用于区分密切相关的HLA - A2分子上的免疫原性细胞表位和血清学表位。根据突变型和亚型HLA - A2分子中已知的序列变化,似乎跨越第147至157位氨基酸残基的序列对于该I类MHC分子的细胞识别可能至关重要。

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