Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.
Limiting dilution comparison of the repertoires of high and low responder MHC-restricted T cells.
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DOI：
10.1084/jem.167.3.1100
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发表时间：
1988-03-01
期刊：
影响因子：
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通讯作者：
Berzofsky JA
中科院分区：
文献类型：
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作者：
Kojima M;Cease KB;Buckenmeyer GK;Berzofsky JA
为了探讨ir基因控制的对整个蛋白质，如抹香鲸肌红蛋白(SWMb)的高反应性或低反应性的机制，我们通过极限稀释频率分析比较了不同肌红蛋白表位的高、低反应性单倍型限制性T细胞的谱系。泊松分析使用长期极限稀释细胞系(B10.BR[低]X B10.D2[高])F1 T细胞，维持在高或低应答APC上。用SWMb多肽和片段检测T细胞系的精细特异性和Ia限制。B10.BR(H-2k)APC对SWMb特异性F1 T细胞的反应率比B10.D2(H-2d)APC低2.5-3.6倍。值得注意的是，所有H-2k限制性T细胞都以I-Ek为限制性元件，而在H-2d限制性T细胞系中既有I-Ad-限制性T细胞，也有I-Ed限制性T细胞。I-Ad限制性T细胞占优势，大多数是合成肽102-118的特异性T细胞。多肽132-146的特异性T细胞较少，主要与I-ED相关。然而，没有可检测到的H-2k限制性T细胞对这两种多肽中的任何一种是特异的，相反，它们是对片段1-55或多肽59-80特异的。片段1-55也刺激了类似数量的H-2d限制性T细胞。因此，F1 T细胞对H-2k提呈细胞的低反应可能是由于未能看到肌红蛋白与I-AK结合，特别是Glu 109周围的免疫优势部位，而高应答小鼠(H-2d和H-2s)的优势反应集中在I-A分子和Glu 109残基周围。I-E-Low Responder B10菌株也未能对肽102-118产生反应，支持了低响应者状态是由于对102-118加I-A缺乏反应所致的有限谱系的观点。在那些对免疫优势位点102-118有反应的菌株中，该位点特异性谱系中T细胞的频率总是显著高于其他位点。这些结果表明，免疫优势表位和次要表位之间有一个重要的区别，ir基因控制的对天然完整蛋白的低反应性可能主要是由于未能对单个免疫优势位点做出反应，尽管可以识别许多其他表位。
To approach the mechanism that determines Ir gene-controlled high or low responsiveness to whole proteins, such as sperm whale myoglobin (SWMb), we compared the repertoires of high and low responder haplotype- restricted T cells for different myoglobin epitopes by limiting dilution frequency analysis. Poisson analysis was performed using long- term limiting dilution cell lines of (B10.BR [low] X B10.D2[high])F1 T cells maintained on high or low responder APCs. The cell lines were tested with SWMb peptides and fragments for T cell repertoire fine specificities and Ia restrictions. The frequency of SWMb-specific F1 T cells responsive on B10.BR (H-2k) APCs was 2.5-3.6-fold lower than on B10.D2 (H-2d) APCs. Strikingly, all of the H-2k-restricted T cells used I-Ek as a restriction element, whereas both I-Ad- and I-Ed-restricted T cells were found among the H-2d-restricted lines. The I-Ad-restricted T cells were dominant, and the majority was specific for the synthetic peptide 102-118. T cells specific for peptide 132-146, dominant in association with I-Ed, were less frequent. However, no detectable H-2k- restricted T cells were specific for either of these peptides, but instead they were specific for fragment 1-55 or peptide 59-80. Fragment 1-55 also stimulated a similar number of H-2d-restricted T cells. Therefore, the low response of F1 T cells on H-2k-presenting cells may be due to the failure to see myoglobin plus I-Ak, in particular the immunodominant site around Glu 109, in contrast to the dominant response of high responder mice (both H-2d and H-2s) focused on the I-A molecule and the site around residue Glu 109. The I-E- low responder B10 strain also failed to respond to peptide 102-118, supporting the idea that the low responder status results from a limited repertoire lacking response to 102-118 plus I-A. In those strains that respond to the immunodominant site 102-118, the frequency of T cells in the repertoire specific for this site was always considerably greater than that for other sites. These results suggest that there is an important difference between immunodominant epitopes and minor epitopes and that Ir gene-controlled low responsiveness to a natural whole protein may be due primarily to the failure to respond to a single immunodominant site, even though a number of other epitopes can be recognized.