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小鼠抗HLA - DQ3单克隆抗体的独特型多样性和可变区基因使用情况

Idiotypic diversity and variable region gene usage by mouse anti-HLA-DQ3 mAb.

作者信息

Iwasaki Y, Takabatake H, Monestier M, Ferrone S

机构信息

Department of Microbiology and Immunology, New York Medical College, Valhalla 10595, USA.

出版信息

Immunogenetics. 1995;42(2):90-100. doi: 10.1007/BF00178583.

DOI:10.1007/BF00178583
PMID:7607710
Abstract

The anti-HLA-DQ3 monoclonal antibodies (mAb) KS13, SO1, SO2, SO3, SO4, and SO5 recognize spatially close but distinct antigenic determinants, since they crossinhibit each other in their binding to HLA-DQ3 antigens, but do not share idiotopes recognized in their antigen combining site by syngeneic and anti-id antisera and mAb. Furthermore, mAb SO1, SO3, SO4, and SO5 react also with HLA-DQ allospecificities other than HLA-DQ3. Sequence analysis of the heavy (VH) and light (VL) chain variable region of the six mAb revealed preferential usage of VH 36-60 and VK 12/13 gene families. However, the individual VH and VL germline gene usage by the six mAb is diverse and the utilization of D, JH, and JL gene segments is heterogeneous. The diverse usage of VH and VL gene segments and heterogeneous amino acid sequences of VH and VL CDR, together with the heterogeneous idiotypic profile, may reflect the complexity of the determinants recognized by the six mAb on HLA-DQ3 antigens. The results we have presented provide for the first time information about the structural basis of the diversity of antibodies recognizing human histocompatibility antigens.

摘要

抗HLA - DQ3单克隆抗体(mAb)KS13、SO1、SO2、SO3、SO4和SO5识别空间上紧密相邻但不同的抗原决定簇,因为它们在与HLA - DQ3抗原结合时相互交叉抑制,但不共享同基因和抗独特型抗血清及单克隆抗体在其抗原结合位点识别的独特型。此外,单克隆抗体SO1、SO3、SO4和SO5还与HLA - DQ3以外的HLA - DQ同种特异性反应。对这六种单克隆抗体的重链(VH)和轻链(VL)可变区进行序列分析,发现优先使用VH 36 - 60和VK 12/13基因家族。然而,这六种单克隆抗体对各个VH和VL种系基因的使用是多样的,并且D、JH和JL基因片段的利用是异质性的。VH和VL基因片段的多样使用以及VH和VL互补决定区(CDR)的异质氨基酸序列,连同异质性独特型谱,可能反映了这六种单克隆抗体在HLA - DQ3抗原上识别的决定簇的复杂性。我们给出的结果首次提供了关于识别人类组织相容性抗原的抗体多样性结构基础的信息。

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