DEGENERACY OF T-CELL RECEPTOR RECOGNITION OF AN INFLUENZA-VIRUS HEMAGGLUTININ EPITOPE RESTRICTED BY HLA-DQ AND HLA-DR CLASS-II MOLECULES
DEGENERACY OF T-CELL RECEPTOR RECOGNITION OF AN INFLUENZA-VIRUS HEMAGGLUTININ EPITOPE RESTRICTED BY HLA-DQ AND HLA-DR CLASS-II MOLECULES
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DOI：
10.1002/eji.1830240519
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发表时间：
1994-05-01
影响因子：
5.4
通讯作者：
FAITH, A
中科院分区：
文献类型：
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作者：
JONES, CM;LAKE, RA;FAITH, A
T细胞受体(TCR)识别与主要组织相容性(MHC)分子结合的短肽形式的抗原。TCR具有免疫球蛋白(Ig)样的结构，与Ig识别抗原的方式类似，TCR的第三互补决定区(CDR3)被认为提供了与位于MHC沟中的多肽的主要接触。CDR1和CDR2被认为与呈递的MHC分子接触。我们已经分析了七个识别流感病毒血凝素(H3)HA1亚基中保守的多肽表位(残基255-270)的人CD4+T细胞克隆。两个T细胞克隆分别在HLA-DRB1*1001和HLA-DQB1*0602/DQA1*0102的背景下识别该肽，并共享V-α、V-β和J(β)基因片段。只有编码两个TCR链的CDR3区的连接区不同。这表明这些TCR的CDR3区域与MHC II类分子相互作用。有6个T细胞克隆受到人类白细胞抗原DRB1*1001的限制。其中2个克隆表达V(Beta)9.1，3个表达V(Beta)13基因片段；其余克隆表达V(Beta)7.2，与V(Beta)9.1同源。V-α和J基因片段的多样化选择导致了TCR的连接异质性，表明识别表位的序列组合的多样性。然而，6个T细胞克隆中有5个在V-αCDR3环中带有一个基序，由相邻的酸性和极性氨基酸残基组成，每个CDR3的羧基末端有8个残基。
The T cell receptor (TcR) recognizes antigens in the form of short peptide fragments bound to major histocompatibility (MHC) molecules. TcR have an immunoglobulin (Ig)-like structure and, in an analogous manner to antigen recognition by Ig, the third complementarity determining regions (CDR3) of the TcR are believed to provide the primary contact with the peptide lying in the MHC groove. CDR1 and CDR2 are thought to contact the presenting MHC molecule. We have analyzed seven human CD4+ T cell clones that recognize a conserved peptide epitope (residues 255-270) within the influenza virus hemagglutinin (H3) HA1 subunit. Two T cell clones recognized the peptide in the context of HLA-DRB1*1001 and HLA-DQB1* 0602/DQA1*0102, respectively, and shared V-alpha,V-beta and J(beta) gene segments. Only the junctional regions encoding the CDR3 regions of the two TcR chains were different. This suggests that the CDR3 regions of these TcR interact with the MHC class II molecule. Six of the Tcell clones were restricted by the HLA-DRB1*1001. Two of these Tcell clones expressed V(beta)9.1 and three expressed V(beta)13 gene segments; the remaining clone expressed V(beta)7.2, a close homologue of V(beta)9.1. A diverse selection of V-alpha and J gene segments contributed to the junctional heterogeneity of the TcR, indicating a diversity of sequence combinations recognizing the epitope. Nevertheless, five out of six T cell clones bore a motif in the V-alpha CDR3 loop consisting of adjacent acidic and polar amino acid residues, eight residues from the carboxyl end of each CDR3.