Clustering HLA class I superfamilies using structural interaction patterns

PLoS One. 2014 Jan 27;9(1):e86655. doi: 10.1371/journal.pone.0086655. eCollection 2014.

Abstract

Human leukocyte antigen (HLA) class I molecules are critical components of the cell-mediated immune system that bind and present intracellular antigenic peptides to CD8(+) T cell receptors. To understand the interaction mechanism underlying human leukocyte antigen (HLA) class I specificity in detail, we studied the structural interaction characteristics of 16,393 nonameric peptides binding to 58 HLA-A and -B molecules. Our analysis showed for the first time that HLA-peptide intermolecular bonding patterns vary among different alleles and may be grouped in a superfamily dependent manner. Through the use of these HLA class I 'fingerprints', a high resolution HLA class I superfamily classification schema was developed. This classification is capable of separating HLA alleles into well resolved, non-overlapping clusters, which is consistent with known HLA superfamily definitions. Such structural interaction approach serves as an excellent alternative to the traditional methods of HLA superfamily definitions that use peptide binding motifs or receptor information, and will help identify appropriate antigens suitable for broad-based subunit vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cluster Analysis
  • Computational Biology
  • Epitopes, T-Lymphocyte / metabolism
  • HLA-A Antigens / classification*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism*
  • HLA-B Antigens / classification*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / metabolism*
  • Humans
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Peptides / metabolism*
  • Protein Binding

Substances

  • Epitopes, T-Lymphocyte
  • HLA-A Antigens
  • HLA-B Antigens
  • Peptides

Grant support

This study was supported by the intramural research funds by Agency for Science, Technology and Research (A*STAR), and also by A*STAR’s Joint Council Office (JCO) Research Grant (grant number: CCOGA02_008_2008). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.