Identifiying Human MHC Supertypes Using Bioinformatic Methods
| Autor: | Irini Doytchinova, Darren R. Flower, Pingping Guan |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Amino Acid Motifs
Immunology Population Peptide binding HLA-C Antigens Human leukocyte antigen Computational biology Major histocompatibility complex Mhc polymorphism Epitope HLA Antigens Protein Interaction Mapping Molecular interaction fields Humans Immunology and Allergy education Alleles Genetics education.field_of_study Binding Sites HLA-A Antigens biology Histocompatibility Testing Histocompatibility Antigens Class I Computational Biology DNA Fingerprinting HLA-B Antigens Multigene Family biology.protein |
| Zdroj: | The Journal of Immunology. 172:4314-4323 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.172.7.4314 |
| Popis: | 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 Tyr9/Phe9, Arg97, and His114 or Tyr116; the A3-Tyr9/Phe9/Ser9, Ile97/Met97 and Glu114 or Asp116; the A24-Ser9 and Met97; the B7-Asn63 and Leu81; the B27-Glu63 and Leu81; for B44-Ala81; the C1-Ser77; and the C4-Asn77. action 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 Tyr9/Phe9, Arg97, and His114 or Tyr116; the A3-Tyr9/Phe9/Ser9, Ile97/Met97 and Glu114 or Asp116; the A24-Ser9 and Met97; the B7-Asn63 and Leu81; the B27-Glu63 and Leu81; for B44-Ala81; the C1-Ser77; and the C4-Asn77. |
| Databáze: | OpenAIRE |
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