The peptide-binding specificity of HLA-A*3001 demonstrates membership of the HLA-A3 supertype

Immunogenetics. 2008 Nov;60(11):633-43. doi: 10.1007/s00251-008-0317-z. Epub 2008 Sep 4.

Abstract

Human leukocyte antigen class I (HLA-I) molecules are highly polymorphic peptide receptors, which select and present endogenously derived peptide epitopes to CD8+ cytotoxic T cells (CTL). The specificity of the HLA-I system is an important component of the overall specificity of the CTL immune system. Unfortunately, the large and rapidly increasing number of known HLA-I molecules seriously complicates a comprehensive analysis of the specificities of the entire HLA-I system (as of June 2008, the international HLA registry holds >1,650 unique HLA-I protein entries). In an attempt to reduce this complexity, it has been suggested to cluster the different HLA-I molecules into "supertypes" of largely overlapping peptide-binding specificities. Obviously, the HLA supertype concept is only valuable if membership can be assigned with reasonable accuracy. The supertype assignment of HLA-A*3001, a common HLA haplotype in populations of African descent, has variously been assigned to the A1, A3, or A24 supertypes. Using a biochemical HLA-A*3001 binding assay, and a large panel of nonamer peptides and peptide libraries, we here demonstrate that the specificity of HLA-A*3001 most closely resembles that of the HLA-A3 supertype. We discuss approaches to supertype assignment and underscore the importance of experimental verification.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Combinatorial Chemistry Techniques
  • Genes, MHC Class I*
  • HLA-A Antigens / chemistry*
  • HLA-A Antigens / genetics
  • HLA-A Antigens / metabolism
  • Humans
  • Multigene Family
  • Oligopeptides / metabolism*
  • Peptide Library
  • Phylogeny
  • Protein Binding
  • Substrate Specificity

Substances

  • HLA-A Antigens
  • Oligopeptides
  • Peptide Library