Dietrich P Y, Walker P R, Quiquerez A L, Perrin G, Dutoit V, Liénard D, Guillaume P, Cerottini J C, Romero P, Valmori D
Division of Oncology, University Hospital, Geneva, Switzerland.
Cancer Res. 2001 Mar 1;61(5):2047-54.
HLA-A2+ melanoma patients develop naturally a strong CD8+ T cell response to a self-peptide derived from Melan-A. Here, we have used HLA-A2/peptide tetramers to isolate Melan-A-specific T cells from tumor-infiltrated lymph nodes of two HLA-A2+ melanoma patients and analyzed their TCR beta chain V segment and complementarity determining region 3 length and sequence. We found a broad diversity in Melan-A-specific immune T-cell receptor (TCR) repertoires in terms of both TCR beta chain variable gene segment usage and clonal composition. In addition, immune TCR repertoires selected in the patients were not overlapping. In contrast to previously characterized CD8+ T-cell responses to viral infections, this study provides evidence against usage of highly restricted TCR repertoire in the natural response to a self-differentiation tumor antigen.
HLA - A2阳性的黑色素瘤患者会自然地对源自黑色素瘤抗原A（Melan - A）的自身肽产生强烈的CD8 + T细胞反应。在此，我们使用HLA - A2/肽四聚体从两名HLA - A2阳性黑色素瘤患者的肿瘤浸润淋巴结中分离出Melan - A特异性T细胞，并分析了它们的TCRβ链V区片段、互补决定区3的长度和序列。我们发现，就TCRβ链可变基因片段的使用和克隆组成而言，Melan - A特异性免疫T细胞受体（TCR）库具有广泛的多样性。此外，两名患者中选择的免疫TCR库并不重叠。与先前表征的针对病毒感染的CD8 + T细胞反应不同，本研究提供了证据，反对在对自身分化肿瘤抗原的天然反应中使用高度受限的TCR库。
