Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains.
Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains.
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DOI：
10.4049/jimmunol.152.1.163
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发表时间：
1994-01
影响因子：
4.4
通讯作者：
Kevin C. H. Parker;M. Bednarek;J. Coligan
中科院分区：
文献类型：
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作者：
Kevin C. H. Parker;M. Bednarek;J. Coligan
基于实验肽结合数据，开发了一种预测所有可能的非肽与MHC I类分子HLA-A2的相对结合强度的方法。这些数据表明，对于大多数肽，肽的每个侧链都对HLA-A2复合物的稳定性有一定的贡献，而这种稳定性与肽的序列无关。为了量化这些贡献，我们将154个肽的结合数据组合在一起，生成一个包含180个系数（20个氨基酸x 9个位置）的表，每个系数代表肽中特定位置的一个特定氨基酸残基对HLA-A2结合的贡献。80多肽形成稳定的HLA-A2复合物，通过测量β 2m的解离率来评估。其余74个多肽形成复合物，在37℃下β 2m解离的半衰期小于5分钟，或者不与HLA-A2结合，这些复合物被包括在内，因为它们可以用来约束某些系数的值。“理论”结合稳定性（通过将相应系数相乘计算）与实验结合稳定性的匹配程度在5倍之内。然后使用这些系数来计算所有先前鉴定的已知与HLA-A2结合的自身或抗原非特异性肽的理论结合稳定性。此外，还预测了所有其他非聚合体肽的结合稳定性，这些非聚合体肽可以由这些蛋白质衍生而来。在每种情况下，先前描述的HLA-A2结合肽在每种源蛋白的所有可能的佚名中都排在前2%。因此，大多数生物学上相关的高分子肽应该使用系数表来识别。我们得出的结论是，大多数非聚合肽的侧链与HLA-A2分子相互独立地结合。
A method to predict the relative binding strengths of all possible nonapeptides to the MHC class I molecule HLA-A2 has been developed based on experimental peptide binding data. These data indicate that, for most peptides, each side-chain of the peptide contributes a certain amount to the stability of the HLA-A2 complex that is independent of the sequence of the peptide. To quantify these contributions, the binding data from a set of 154 peptides were combined together to generate a table containing 180 coefficients (20 amino acids x 9 positions), each of which represents the contribution of one particular amino acid residue at a specified position within the peptide to binding to HLA-A2. Eighty peptides formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation of beta 2m. The remaining 74 peptides formed complexes that had a half-life of beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA-A2, and were included because they could be used to constrain the values of some of the coefficients. The "theoretical" binding stability (calculated by multiplying together the corresponding coefficients) matched the experimental binding stability to within a factor of 5. The coefficients were then used to calculate the theoretical binding stability for all the previously identified self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability for all other nonamer peptides that could be generated from the proteins from which these peptides were derived was also predicted. In every case, the previously described HLA-A2 binding peptides were ranked in the top 2% of all possible nonamers for each source protein. Therefore, most biologically relevant nonamer peptides should be identifiable using the table of coefficients. We conclude that the side-chains of most nonamer peptides to the first approximation bind independently of one another to the HLA-A2 molecule.