Hawes G E, Struyk L, Beacock-Sharp H, Henwood J, Hill Gaston J S, van den Elsen P J
Department of Immunohematology and Blood Bank, Leiden University Medical Center, The Netherlands.
Immunogenetics. 1998 Aug;48(3):196-201. doi: 10.1007/s002510050423.
Previously we have shown that the T-cell response against the HLA-DR3 (17)-restricted heat shock protein (Mr 65 000)-derived peptide amino acids (aa) 3-13 (hsp65 aa 3-13) is recognized by the exclusive usage of the TRBV5 gene as well as a conserved CDR3 region in a tuberculoid leprosy patient. In the present study we analyzed the TcR of T-cell clones specific for hsp65 aa 3-13 derived from three healthy individuals with a response level similar to that of the leprosy patient. We show that unlike the tuberculoid leprosy patient, healthy high responders have a diverse T-cell response to hsp65 aa 3-13. However, a striking observation was made: even though high responders have a diverse specific TcR repertoire, TRBV5-expressing clones from two healthy individuals could be isolated that were nearly identical to a dominant clone in the tuberculoid leprosy patient. In conclusion, the data show that restriction of TcR specific for an antigen correlates with the presence of that antigen in disease. However, the preferred TcR can also be detected in healthy high responders. A natural infection in vivo, as with the tuberculoid leprosy patient, may be responsible for the observed trimming and preferential outgrowth of a certain TcR.
此前我们已经表明，在一名结核样型麻风患者中，针对HLA - DR3(17)限制性热休克蛋白（分子量65000）衍生肽氨基酸（aa）3 - 13（hsp65 aa 3 - 13）的T细胞应答通过TRBV5基因的独特使用以及保守的互补决定区3被识别。在本研究中，我们分析了来自三名健康个体的对hsp65 aa 3 - 13特异的T细胞克隆的T细胞受体，其应答水平与该麻风患者相似。我们发现，与结核样型麻风患者不同，健康的高应答者对hsp65 aa 3 - 13有多样的T细胞应答。然而，有一个惊人的发现：尽管高应答者有多样的特异性T细胞受体库，但可以从两名健康个体中分离出表达TRBV5的克隆，它们几乎与结核样型麻风患者中的一个优势克隆相同。总之，数据表明针对一种抗原的T细胞受体的限制性与该抗原在疾病中的存在相关。然而，在健康的高应答者中也能检测到偏好的T细胞受体。体内的自然感染，如结核样型麻风患者的情况，可能是观察到的特定T细胞受体的修剪和优先增殖的原因。
