Garrido Pilar, Ruiz-Cabello Francisco, Bárcena Paloma, Sandberg Yorick, Cantón Julia, Lima Margarida, Balanzategui Ana, González Marcos, López-Nevot Miguel Angel, Langerak Anton W, García-Montero Andrés C, Almeida Julia, Orfao Alberto
Servicio de Hematología, Hospital Universitario Virgen de las Nieves, Granada, Spain.
Blood. 2007 Jun 1;109(11):4890-8. doi: 10.1182/blood-2006-05-022277. Epub 2007 Feb 15.
Monoclonal TCRalphabeta(+)/CD4+ T-large granular lymphocyte (T-LGL) lymphocytosis is a T-cell disorder with a restricted TCR-Vbeta repertoire. In the present study we explored the potential association between the expanded TCR-Vbeta families, the CDR3 sequences of the TCR-Vbeta gene, and the HLA genotype of patients with monoclonal TCRalphabeta(+)/CD4+ T-LGL lymphocytosis. For that purpose, 36 patients with monoclonal TCRalphabeta(+)/CD4+ T-LGL lymphocytosis (15 TCR-Vbeta13.1 versus 21 non-TCR-Vbeta13.1) were selected. For each patient, both the HLA (class I and II) genotype and the DNA sequences of the VDJ-rearranged TCR-Vbeta were analyzed. Our results show a clear association between the TCR-Vbeta repertoire and the HLA genotype, all TCR-Vbeta13.1(+) cases being HLA-DRB1*0701 (P = .004). Interestingly, the HLA-DR7/TCR-Vbeta13.1-restricted T-cell expansions displayed a highly homogeneous and strikingly similar TCR arising from the use of common TCR-Vbeta gene segments, which shared (1) unique CDR3 structural features with a constantly short length, (2) similar combinatorial gene rearrangements with frequent usage of the Jbeta1.1 gene, and (3) a homolog consensus protein sequence at recombination junctions. Overall, these findings strongly support the existence of a common antigen-driven origin for monoclonal CD4+ T-LGL lymphocytosis, with the identification of the exact peptides presented to the expanded T cells deserving further investigations.
单克隆TCRαβ(+)/CD4+大颗粒淋巴细胞(T-LGL)淋巴细胞增多症是一种T细胞疾病，其TCR-Vβ库有限。在本研究中，我们探讨了单克隆TCRαβ(+)/CD4+ T-LGL淋巴细胞增多症患者中扩增的TCR-Vβ家族、TCR-Vβ基因的CDR3序列与HLA基因型之间的潜在关联。为此，选择了36例单克隆TCRαβ(+)/CD4+ T-LGL淋巴细胞增多症患者(15例TCR-Vβ13.1阳性与21例非TCR-Vβ13.1阳性)。对每位患者的HLA(Ⅰ类和Ⅱ类)基因型以及VDJ重排的TCR-Vβ的DNA序列进行了分析。我们的结果显示TCR-Vβ库与HLA基因型之间存在明显关联，所有TCR-Vβ13.1(+)病例均为HLA-DRB1*0701(P = .004)。有趣的是，HLA-DR7/TCR-Vβ13.1限制性T细胞扩增显示出高度同源且惊人相似的TCR，这是由于使用了共同的TCR-Vβ基因片段，这些片段具有(1)独特的CDR3结构特征，长度恒定较短，(2)相似的组合基因重排，频繁使用Jβ1.1基因，以及(3)重组连接处的同源共有蛋白序列。总体而言，这些发现有力地支持了单克隆CD4+ T-LGL淋巴细胞增多症存在共同抗原驱动起源的观点，确定呈递给扩增T细胞的精确肽值得进一步研究。
