Identifiying human MHC supertypes using bioinformatic methods
Identifiying human MHC supertypes using bioinformatic methods
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DOI：
10.4049/jimmunol.172.7.4314
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发表时间：
2004-04-01
影响因子：
4.4
通讯作者：
Flower, DR
中科院分区：
文献类型：
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作者：
Doytchinova, IA;Guan, PP;Flower, DR
根据多肽结合特异性将MHC分子分类为超型是一个重要问题，对开发具有广泛人群覆盖的基于表位的疫苗具有直接意义。由于MHC多态性极高（948个I类和633个II类HLA等位基因），目前还无法通过实验解决这一问题。在这项研究中，我们描述了一个生物信息学；利用仅从三维蛋白质结构中提取的信息将MHC分子分类为超型的策略。两种化学计量学技术——分层聚类和主成分分析——分别应用于783个HLA I类分子，根据结构相似性和肽结合位点计算的分子相互作用场来确定超型。定义了8个超型：A2、A3、A24、B7、B27、B44、C1和C4。两种方法的一致性为77%，即605个HLA I类等位基因均属于同一超型。提出的策略允许“超型指纹”被识别。因此，A2超型指纹图谱为Tyr(9)/Phe(9)、Arg（97）、His（114）或Tyr(116)；A3-Tyr(9)/Phe(9)/Ser(9)、Ile(97) /Met（97）、Glut（114）或Asp(116)；A24-Ser(9)和Met(97)；B7-Asn（63）和Leu(81)；B27-Glu（63）和Leu(81)；B44-Ala (81);C1-Ser (77);C4-Asn（77）。
Classification of MHC molecules into supertypes in terms of peptide-binding specificities is an important issue, with direct implications for the development of epitope-based vaccines with wide population coverage. In view of extremely high MHC polymorphism (948 class I and 633 class II HLA alleles) the experimental solution of this task is presently impossible. In this study, we describe a bioinformatics; strategy for classifying MHC molecules into supertypes using information drawn solely from three-dimensional protein structure. Two chemometric techniques-hierarchical clustering and principal component analysis-were used independently on a set of 783 HLA class I molecules to identify supertypes based on structural similarities and molecular interaction fields calculated for the peptide binding site. Eight supertypes were defined: A2, A3, A24, B7, B27, B44, C1, and C4. The two techniques gave 77% consensus, i.e., 605 HLA class I alleles were classified in the same supertype by both methods. The proposed strategy allowed "supertype fingerprints" to be identified. Thus, the A2 supertype fingerprint is Tyr(9)/Phe(9), Arg(97), and His(114) or Tyr(116); the A3-Tyr(9)/Phe(9)/Ser(9), Ile(97) /Met(97) and Glut(114) or Asp(116); the A24-Ser(9) and Met(97); the B7-Asn(63) and Leu(81); the B27-Glu(63) and Leu(81); for B44-Ala(81); the C1-Ser(77); and the C4-Asn(77).