On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.
On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.
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DOI：
10.4049/jimmunol.147.8.2663
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发表时间：
1991-10
影响因子：
4.4
通讯作者：
D. O'Sullivan;Thomas S. Arrhenius;J. Sidney;M. D. Guercio;M. Albertson;M. Wall;C. Oseroff;S. Southwood;S. Colon;F. Gaeta
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文献类型：
--
作者：
D. O'Sullivan;Thomas S. Arrhenius;J. Sidney;M. D. Guercio;M. Albertson;M. Wall;C. Oseroff;S. Southwood;S. Colon;F. Gaeta
我们研究了 DR1 分子与两种抗原肽（破伤风类毒素 830-843 和血凝素 307-319）之间的相互作用，此前已知这两种抗原肽可结合大多数 DR 等位基因（简并结合），并在不同 DR 等位基因的背景下被相同的 T 细胞克隆识别（混杂 T 细胞识别）。将这两种肽的 DR1 亲和力与其他两种不同的 T 细胞表位（百日咳毒素 30-42 和豚草过敏原 Ra3 51-65）进行比较。研究发现，简并性和混杂性与高亲和力相互作用相关，而结合和 T 细胞选择性与较弱的相互作用相关。因此，正如通常在抗体分子中观察到的那样，DR-肽相互作用的选择性似乎与亲和力成反比。还测试了血凝素 307-319 决定簇的几种单取代类似物结合各种 DR 等位基因（DR1、DR2、DR5 和 DR7）的能力。获得的结果表明该决定簇可能以相似的方向结合不同的 DR 等位基因。当按照相同的实验方法研究破伤风类毒素 830-843 决定簇与三个不同 DR 等位基因（DR1、DR2 和 DR7）之间的相互作用时，得出了类似的结论。当比较这两种肽的关键 DR 结合残基时，发现它们在化学性质和肽一级结构中的间距方面非常相似，表明这两种肽可能以非常相似的方向结合 DR。最后，推定基序已被推导并显示存在于大多数测试的 DR 结合剂中，但仅存在于少数非 DR 结合肽中。
We have investigated the interaction between DR1 molecules and the two antigenic peptides, tetanus toxoid 830-843 and hemagglutinin 307-319, previously known to bind most DR alleles (degenerate binding) and to be recognized by the same T cell clones in the context of different DR alleles (promiscuous T cell recognition). The DR1 affinity of these two peptides was compared with that of two other different T cell epitopes (pertussis toxin 30-42 and ragweed allergen Ra3 51-65). It was found that degeneracy and promiscuity were associated with high affinity interactions, whereas binding and T cell selectivity were associated with weaker interactions. Thus, the selectivity of DR-peptide interactions, as is commonly observed with the antibody molecule, appears to be inversely correlated to affinity. Several singly substituted analogs of the hemagglutinin 307-319 determinant have also been tested for capacity to bind various DR alleles (DR1, DR2, DR5, and DR7). The results obtained suggest that this determinant may bind the different DR alleles in a similar orientation. Similar conclusions were reached when the interaction between the tetanus toxoid 830-843 determinant and three different DR alleles (DR1, DR2, and DR7) was studied following the same experimental approach. When crucial DR-binding residues of the two peptides were compared, it was found that they were very similar in both chemical nature and spacing in the peptide primary structure, suggesting that the two peptides may bind DR in a very similar orientation. Finally, a putative motif has been derived and shown to be present in a majority of the DR binders tested, but only in a minority of the non-DR binding peptides.