Conserved CDR3 regions in T-cell receptor (TCR) CD8+ T cells that recognize the Tax11-19/HLA-A*0201 complex in a subject infected with human T-Cell leukemia virus type 1:: Relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure
Conserved CDR3 regions in T-cell receptor (TCR) CD8+ T cells that recognize the Tax11-19/HLA-A*0201 complex in a subject infected with human T-Cell leukemia virus type 1:: Relationship of T-cell fine specificity and major histocompatibility complex/peptide/TCR crystal structure
复制标题
DOI：
10.1128/jvi.75.20.9836-9843.2001
复制
发表时间：
2001-10-01
影响因子：
5.4
通讯作者：
Hafler, DA
中科院分区：
文献类型：
--
作者：
Bourcier, KD;Lim, DG;Hafler, DA
我们研究了 CD8+ T 细胞的 T 细胞受体 (TCR) 库，这些细胞识别由人 T 细胞白血病病毒 (HTLV-1) 表达的 Tax 蛋白的 Tax11-19 免疫显性表位，该病毒与 HTLV-1 相关脊髓病 (HAM/TSP) 疾病有关。一组 Tax11-19 反应性 CD8(+) T 细胞克隆是通过单细胞克隆来自 HTLV-1 感染个体的 Tax11-19/HLA-A*0201 四聚体阳性外周血淋巴细胞而产生的。 TCR 使用分析表明，不同 TCR α 和 β 链的组合可用于识别 Tax11-19，但主要 T 细胞克隆群（24 个克隆中的 15 个）表达 TCR V β 13S1 和 V α 17 链。我们发现我们的主要 CD8(+) T 细胞克隆组与先前报道的源自不同受试者的 TCR 克隆（包括具有解析晶体结构的 TCR）之间，TCR α 和 β 链的 CDR3 区域具有惊人的相似性。 V β 链 CDR3 区中的 3 个氨基酸序列 (PG-G) 在表达 V β 13S1 和 V α 17 链的所有 Tax11-19 反应性 T 细胞克隆中是保守的。 CDR3 区域中的保守氨基酸不直接接触 Tax11-19 肽，B7-TCR 的晶体结构证实了这一点，B7-TCR 是一种与本研究中分离的 VB13S1 克隆几乎相同的 TCR。使用 Tax11-19 的改变的肽配体 (APL) 进行的精细肽特异性分析揭示了这组 T 细胞克隆之间的相似识别模式。这些数据表明 CDR3 β 环中的 PG-G 氨基酸提供了维持 TCR 三级结构所需的结构框架。
We investigated the T-cell receptor (TCR) repertoire of CD8(+) T cells that recognize the Tax11-19 immunodominant epitope of Tax protein expressed by human T-cell leukemia virus (HTLV-1) that is implicated in the disease HTLV-1-associated myelopathy (HAM/TSP). A panel of Tax11-19-reactive CD8(+) T-cell clones was generated by single-cell cloning of Tax11-19/HLA-A*0201 tetramer-positive peripheral blood lymphocytes from an HTLV-1-infected individual. The analyses of TCR usage revealed that the combination of diverse TCR alpha and beta chains could be used for the recognition of Tax11-19 but the major population of T-cell clones (15 of 24 clones) expressed the TCR V beta 13S1 and V alpha 17 chain. We found striking similarities in CDR3 regions of TCR alpha and beta chains between our major group of CD8(+) T-cell clones and those originating from different subjects as previously reported, including TCRs with resolved crystal structures. A 3-amino-acid sequence (PG-G) in the CDR3 region of the V beta chain was conserved among all the Tax11-19-reactive T-cell clones expressing V beta 13S1 and V alpha 17 chains. Conserved amino acids in the CDR3 region do not directly contact the Tax11-19 peptide, as corroborated by the crystal structure of B7-TCR, a TCR that is almost identical to VB13S1 clones isolated in this study. Analysis of fine peptide specificity using altered peptide ligands (APL) of Tax11-19 revealed a similar recognition pattern among this panel of T-cell clones. These data suggest that the PG-G amino acids in the CDR3 beta loop provide a structural framework necessary for the maintenance of the tertiary TCR structure.