The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides

The presumptive CDR3 regions of both T cell receptor alpha and beta chains determine T cell specificity for myoglobin peptides
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T 细胞受体 α 链和 β 链的假定 CDR3 区域决定了 T 细胞对肌红蛋白肽的特异性

DOI:
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发表时间:
1990
影响因子:
15.3
通讯作者:
C. Fathman
C. Fathman
中科院分区:
医学1区
文献类型:
--
作者:
J. Danska;A. Livingstone;V. Paragas;T. Ishihara;C. Fathman

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T细胞受体α / β (tcr - α / β)由胸腺细胞成熟过程中重组的可变(V)、多样性(D)、连接(J)和恒定(C)片段编码,产生一种赋予T细胞抗原特异性的异源二聚体。与结合游离抗原的免疫球蛋白(igg)不同,tcr - α / β的配体是细胞内降解抗原(即肽)的细胞表面复合物,与主要组织相容性复合物(MHC)的多态产物结合并呈现。因此,T细胞对抗原的识别被定义为MHC受限。基于tcr - α / β V区和Ig Fab氨基酸序列的相似性,以及MHC I类和Ig分子的晶体结构,建立了一个模型。该模型预测互补决定区(CDR) 1和2,由TCR V α和V β片段组成,主要与MHC α螺旋残基接触,而V/J α和V/D/J β连接区(相当于CDR3)与MHC结合槽中的肽接触。由于MHC蛋白的多态性相对于抗原肽的巨大多样性是有限的,TCR可能已经进化到定位高度多样化的连接残基(CDR3),在那里它们与MHC肽槽中结合的抗原有最大的接触。在这里,我们证明了TCR α链和β链中的CDR3序列之间的明确关联,以及使用一组i - ed限制性肌红蛋白反应性T细胞克隆识别抗原精细特异性的差异。这些数据的获取部分依赖于聚合酶链反应的修饰,该反应使用退化的、一致的引物来扩增TCR α链,而无需预先知道它们所利用的V α片段。
The T cell receptor alpha/beta (TCR-alpha/beta) is encoded by variable (V), diversity (D), joining (J), and constant (C) segments assembled by recombination during thymocyte maturation to produce a heterodimer that imparts antigenic specificity to the T cell. Unlike immunoglobulins (Igs), which bind free antigen, the ligands of TCR-alpha/beta are cell surface complexes of intracellularly degraded antigens (i.e., peptides) bound to and presented by polymorphic products of the major histocompatibility complex (MHC). Therefore, antigen recognition by T cells is defined as MHC restricted. A model has been formulated based upon the similarity between TCR-alpha/beta V region and Ig Fab amino acid sequences, and the crystal structure of the MHC class I and Ig molecules. This model predicts that the complementarity determining regions (CDR) 1 and 2, composed of TCR V alpha and V beta segments, primarily contact residues of the MHC alpha helices, whereas V/J alpha and V/D/J beta junctional regions (the CDR3 equivalent) contact the peptide in the MHC binding groove. Because polymorphism in MHC proteins is limited relative to the enormous diversity of antigenic peptides, the TCR may have evolved to position the highly diverse junctional residues (CDR3), where they have maximal contact with antigen bound in the MHC peptide groove. Here, we demonstrate a definitive association between CDR3 sequences in both TCR alpha and beta chains, and differences in recognition of antigen fine specificity using a panel of I-Ed-restricted, myoglobin-reactive T cell clones. Acquisition of these data relied in part upon a modification of the polymerase chain reaction that uses a degenerate, consensus primer to amplify TCR alpha chains without foreknowledge of the V alpha segments they utilize.
T 细胞抗原受体同种异型决定簇特异性鼠单克隆抗体的表征。
DOI: --
发表时间: 1985
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Staerz,UD;Rammensee,HG;Benedetto,JD;Bevan,MJ
通讯作者: Bevan,MJ
两种不同的机制解释了 T 细胞对鸽子细胞色素 c 反应的免疫反应 (Ir) 基因控制。
DOI: --
发表时间: 1988
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
McElligott,DL;Sorger,SB;Matis,LA;Hedrick,SM
通讯作者: Hedrick,SM
C57BL (H-2b) 小鼠胰岛素特异性 T 细胞系的受体多样性。
DOI: --
发表时间: 1987
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Spinella,DG;Hansen,TH;Walsh,WD;Behlke,MA;Tillinghast,JP;Chou,HS;Whiteley,PJ;Kapp,JA;Pierce,CW;Shevach,EM
通讯作者: Shevach,EM