Selection of T lymphocytes bearing limited T-cell receptor beta chains in the response to a human pathogen.
Selection of T lymphocytes bearing limited T-cell receptor beta chains in the response to a human pathogen.
复制标题
选择带有有限 T 细胞受体 β 链的 T 淋巴细胞来响应人类病原体。
DOI：
10.1073/pnas.90.1.188
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发表时间：
1993
影响因子：
11.1
通讯作者：
Modlin,RL
中科院分区：
文献类型：
--
作者：
Wang,XH;Ohmen,JD;Uyemura,K;Rea,TH;Kronenberg,M;Modlin,RL
迟发型超敏反应(DTH)是衡量T细胞对外来抗原反应性的经典指标。为了估计T细胞在对人类病原体的DTH反应中的反应范围，我们测量了T细胞受体(TCR)β链可变区(Vβ)基因在麻风逆转反应中的使用。逆转反应代表麻风自然发生的DTH反应，在这种反应中，T细胞对麻风分枝杆菌的反应增强伴随着细菌从皮损中清除。与同一个体的血液和DTH前病变相比，使用Vβ6、Vβ12、Vβ14和Vβ19编码的TCR的T细胞在患者皮损中的表达显著高于血液和DTH前皮损。此外，这些数据表明，Vβ基因片段在皮损中的优势表达与个体的主要组织相容性复合体II类单倍型之间可能存在关联。Vβ6在4名DR15患者的皮损中显著，DR15是麻风感染的抗性标志。Vβ6TCR的序列分析显示，在逆转反应损伤中，Vβ6.1和Jβ2.7基因片段和V-J连接处的保守氨基酸基序频繁使用，但在同一患者的血液中不使用。浸润性T细胞表达的有限的TCR谱系表明，在对人类病原体的DTH反应中，识别了一组有限的抗原。我们认为，主要组织相容性复合体单倍型影响DTH的机制涉及特定多肽的呈递，随后选择特定的TCR，然后局部寡克隆扩增。
Delayed-type hypersensitivity (DTH) is a classic measure of T-cell responsiveness to foreign antigen. To estimate the extent of the T-cell repertoire in the DTH response to a human pathogen, we measured T-cell receptor (TCR) beta-chain variable-region (V beta) gene usage in reversal reactions in leprosy. Reversal reactions represent naturally occurring DTH responses in leprosy, in which augmentation of T-cell responses to Mycobacterium leprae is concomitant with clearance of bacilli from lesions. T cells using the V beta 6-, V beta 12-, V beta 14-, and V beta 19-encoded TCRs were strikingly overrepresented in the lesions of patients as compared to blood and pre-DTH lesions from the same individuals. Furthermore, these data indicate a possible association between the predominant expression of a V beta gene segment in lesions and the major histocompatibility complex class II haplotype of the individual. V beta 6 was prominent in the lesions of four patients who were DR15, a marker of resistance in leprosy infection. Sequence analysis of V beta 6 TCRs showed frequent use of V beta 6.1 and J beta 2.7 gene segments and a conserved amino acid motif in the V-J junction in a reversal-reaction lesion, but not in blood from the same patient. The limited TCR repertoire expressed by the infiltrating T cells suggests that a limited set of antigens is recognized in the DTH response to a human pathogen. We suggest that the mechanism by which major histocompatibility complex haplotype influences DTH in this disease involves the presentation of specific peptides, with subsequent selection of specific TCRs followed by local oligoclonal expansion.