Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing.
Influences of antigen processing on the expression of the T cell repertoire. Evidence for MHC-specific hindering structures on the products of processing.
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DOI：
10.1084/jem.168.1.357
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发表时间：
1988-07-01
影响因子：
15.3
通讯作者：
BERZOFSKY, JA
中科院分区：
文献类型：
--
作者：
BRETT, SJ;CEASE, KB;BERZOFSKY, JA
在目前的研究中，两条线的证据表明，抗原处理是一个主要因素，除了MHC结合和T细胞库，决定Ir基因的反应性和表位免疫优势。首先，用肌红蛋白序列的合成肽免疫显示了用天然肌红蛋白引发后没有出现的新反应性。例如，对马肌红蛋白免疫的B10.S小鼠（H-2S）主要对肽102-118产生应答，而在用天然马肌红蛋白免疫的B10.BR（H- 2k）小鼠中，对该肽几乎没有应答。然而，在用102-118肽免疫后，两种菌株都对肽有应答。在体外再刺激后，B10.BR T细胞与B10.S T细胞一样应答。类似地，来自两种单倍型小鼠的一些个体102-118特异性T细胞克隆显示出相似的剂量反应和精细的特异性模式。因此，对该位点的低反应性既不是由于库中的漏洞，也不是由于未能与适当的MHC分子结合。另一种解释是，来自肽102-118免疫小鼠的B10.S T细胞对全肌红蛋白的反应几乎与对肽的反应一样好，而来自肽免疫小鼠的B10.BR T细胞虽然对肽反应良好，但对全肌红蛋白的刺激很差。因此，马肌红蛋白的天然加工产物可能在核心表位102-118侧翼的区域中具有阻碍结构，其干扰I-Ak而不是I-AS的呈递。天然肌红蛋白的加工可能影响T细胞反应的表观特异性的第二条证据是使用I-Ad限制性抹香鲸肌红蛋白102-118特异性克隆9.27获得的。这个克隆很容易区分整个抹香鲸肌红蛋白和马肌红蛋白，但它不能区分对应于抹香鲸和马序列的102-118的肽。马肽和天然马肌红蛋白之间的这种区别可以通过用溴化氰人工“加工”马肌红蛋白来克服。在两组实验中，将相同表位良好地呈递给另一单倍型的T细胞的F1 APC未能克服缺陷，因此这不是由于不同单倍型的APC中不同加工的切割片段的可用性，如如果存在MHC连接的加工所预期的。因此，对于I-Ad-和I-Ak-限制性克隆，对肽与天然分子的差异反应似乎取决于所使用的限制性分子。（400字处删节）
Two lines of evidence in the current study indicate that antigen processing is a major factor, in addition to MHC binding and T cell repertoire, that determines Ir gene responsiveness and epitope immunodominance. First, immunization with synthetic peptides of myoglobin sequences revealed new reactivities that had not appeared after priming with native myoglobin. For example, B10.S mice (H-2S) immune to equine myoglobin predominantly responded to peptide 102-118, whereas there was little, if any, response to this peptide in B10.BR (H- 2k) mice immunized with native equine myoglobin. However, after immunization with the 102-118 peptide, both strains responded to the peptide. After in vitro restimulation, B10.BR T cells responded as well as B10.S T cells. Similarly, some individual 102-118-specific T cell clones from mice of both haplotypes showed similar dose responses and fine specificity patterns. Thus, low responsiveness to this site is due neither to a hole in the repertoire nor to a failure to bind to the appropriate MHC molecule. An alternative explanation was suggested by the observation that, whereas B10.S T cells from peptide 102-118-immune mice responded almost as well to whole myoglobin as to the peptide, the B10.BR T cells from peptide immune mice, while responding well to peptide, were poorly stimulated by whole myoglobin. Thus, the product of natural processing of equine myoglobin probably has hindering structures in the regions flanking the core epitope 102-118 that interfere with presentation by I-Ak but not I-AS. The second line of evidence that processing of native myoglobin may influence the apparent specificity of the T cell response was obtained using the I-Ad- restricted sperm whale myoglobin 102-118-specific clone 9.27. This clone discriminated readily between whole sperm whale myoglobin and equine myoglobin, but it did not distinguish between peptides corresponding to 102-118 of the sperm whale and equine sequences. This distinction between equine peptide and native equine myoglobin could be overcome by artificial "processing" of equine myoglobin with cyanogen bromide. In both sets of experiments, F1 APCs that present the same epitope well to T cells of another haplotype failed to overcome the defect, which was therefore not due to the availability of different processed cleavage fragments in APC of different haplotypes, as would be expected if there were MHC-linked processing. Thus, the differential responses to peptides versus native molecule for both I-Ad- and I-Ak- restricted clones appeared to depend on the restricting molecule used.(ABSTRACT TRUNCATED AT 400 WORDS)
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影响因子：
15.3
作者：
Kapp, J A;Pierce, C W;Schlossman, S;Benacerraf, B
通讯作者：
Benacerraf, B
DOI：
10.1073/pnas.84.12.4249
发表时间：
1987-06-01
影响因子：
11.1
作者：
CEASE, KB;MARGALIT, H;BERZOFSKY, JA
通讯作者：
BERZOFSKY, JA
流感病毒部位被特异性H1菌株的鼠辅助T细胞识别。在血凝素分子中定位到九个氨基酸序列。
DOI：
10.1084/jem.158.2.294
发表时间：
1983-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hackett CJ;Dietzschold B;Gerhard W;Ghrist B;Knorr R;Gillessen D;Melchers F
通讯作者：
Melchers F
影响因子：
15.3
作者：
KIMOTO, M;FATHMAN, CG
通讯作者：
FATHMAN, CG
影响因子：
56.9
作者：
GOOD, MF;MALOY, WL;BERZOFSKY, JA
通讯作者：
BERZOFSKY, JA