Immunogenetics

, Volume 48, Issue 5, pp 324–334

A geometric study of the amino acid sequence of class I HLA molecules

  • P. Cano
  • B. Fan
  • Sanford Stass
ORIGINAL PAPER

DOI: 10.1007/s002510050439

Cite this article as:
Cano, P., Fan, B. & Stass, S. Immunogenetics (1998) 48: 324. doi:10.1007/s002510050439

Abstract

HLA class I alleles are studied by representing them in a metric space where each dimension corresponds to each one of the amino acid positions. Their similarity in reference to their ability to present peptides to T cells is then evaluated by calculating the correlation matrix between the amino-acid-composition tables (or binding affinity tables) for the sets of peptides presented by each allele. This correlation matrix is considered an empirical similarity matrix between HLA alleles, and is modeled in terms of possible structures defined in the metric space of HLA class I amino acid sequences. These geometric structures are adequate models of the peptide-binding data currently available. The following clusters of HLA class I molecules are identified in reference to their ability to present peptides: Cluster I) HLA-A3/ HLA-A11/ HLA-A31/ HLA-A33/ HLA-A68; Cluster II) HLA-B35/ HLA-B51/ HLA-B53/ HLA-B54/ HLA-B7; and Cluster III) HLA-A29/ HLA-B61/HLA-B44; the last cluster showing possible similarities between alleles from different loci. In modeling these natural clusters, the geometric structures with more predictive power confirm the importance of those positions in the peptide-binding groove, particularly those in the B pocket. In addition, other positions (46, 79, 113, 131, 144, and 177) appeared to bear some relevance in determining which peptides can be presented by which HLA alleles.

Key words MHCHLA class IPeptide bindingMathematical models

Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • P. Cano
    • 1
  • B. Fan
    • 1
  • Sanford Stass
    • 1
  1. 1.University of Maryland at Baltimore, Department of Pathology, UMMS Clinical Laboratories, 22 S. Greene St., Room N2W50A, Baltimore, MD 21201-1544, USATP