Abstract
The markedly high levels of polymorphism present in classical class I loci of the human major histocompatibility complex have been implicated in infectious and immune disease recognition. The large numbers of alleles present at these loci have, however, limited efforts to verify associations between individual alleles and specific diseases. As an approach to reduce allele diversity to hierarchical evolutionarily related groups, we performed phylogenetic analyses of available HLA-A, B and C allele complete sequences (n = 216 alleles) using different approaches (maximum parsimony, distance-based minimum evolution and maximum likelihood). Full nucleotide and amino acid sequences were considered as well as abridged sequences from the hypervariable peptide binding region, known to interact in vivo, with HLA presented foreign peptide. The consensus analyses revealed robust clusters of 36 HLA-C alleles concordant for full and PBR sequence analyses. HLA-A alleles (n = 60) assorted into 12 groups based on full nucleotide and amino acid sequence which with few exceptions recapitulated serological groupings, however the patterns were largely discordant with clusters prescribed by PBR sequences. HLA-B which has the most alleles (n = 120) and which unlike HLA-A and -C is thought to be subject to frequent recombinational exchange, showed limited phylogenetic structure consistent with recent selection driven retention of maximum heterozygosity and population diversity. Those allele categories recognized offer an explicit phylogenetic criterion for grouping alleles potentially relevant for epidemiologic associations, for inferring the origin of MHC genome organization, and for comparing functional constraints in peptide presentation of HLA alleles.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Corresponding author
Additional information
The publisher or recipient acknowledges the right of the US Government to retain a non-exclusive, royalty-free license in and to any copyright covering the article. This project has been funded in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-56000.
Rights and permissions
About this article
Cite this article
McKenzie, L., Pecon-Slattery, J., Carrington, M. et al. Taxonomic hierarchy of HLA class I allele sequences. Genes Immun 1, 120–129 (1999). https://doi.org/10.1038/sj.gene.6363648
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363648
Keywords
This article is cited by
-
Conserved epitopes with high HLA-I population coverage are targets of CD8+ T cells associated with high IFN-γ responses against all dengue virus serotypes
Scientific Reports (2020)
-
Evolutionary divergence of HLA class I genotype impacts efficacy of cancer immunotherapy
Nature Medicine (2019)
-
Polymorphism of duck MHC class molecules
Immunogenetics (2019)
-
The HLA-B*3906 allele imparts a high risk of diabetes only on specific HLA-DR/DQ haplotypes
Diabetologia (2011)
-
Polymorphic SVA retrotransposons at four loci and their association with classical HLA class I alleles in Japanese, Caucasians and African Americans
Immunogenetics (2010)