Common West African HLA antigens are associated with protection from severe malaria

Hill, Adrian V. S.; Allsopp, Catherine E. M.; Kwiatkowski, Dominic P.; Anstey, Nicholas M.; Twumasi, Patrick; Rowe, Pamela; Bennett, S.C.J.; Brewster, David; McMichael, Andrew J.; Greenwood, Brian

doi:10.1038/352595a0

Cited by 1,435 publications

(930 citation statements)

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“…Previous research with class I loci indicate a correlation between specific alleles and the genetic basis of resistance to particular diseases. [3][4][5][6] However, the relationships uniting each of the alleles at these loci are less clear. Competing processes of selection, recombination, functional constraints, and mutation rates obscure efforts to identify groups of alleles involved with specific diseases.…”

Section: Introductionmentioning

confidence: 99%

Taxonomic hierarchy of HLA class I allele sequences

et al. 1999

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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.

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Section: Introductionmentioning

confidence: 99%

Taxonomic hierarchy of HLA class I allele sequences

et al. 1999

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“…The first peptide (as 8-mer or 9-mer) causes a cytotoxic T lymphocyte (CTL) response whereas the presence of the variant peptides presented by B8 antagonises this same CTL response [19]. HLA B53, a common African allele, which has been shown to be associated with resistance to severe malaria in the Gambia [20], has been crystallized with two 9-mer peptide epitopes, Is6 (KPIVQYDNF) from the malaria parasite P. falciparum [21] and TPYDINQML from the Gag protein of HIV-2 [22]. The related allele HLA B3501 has also been crystallized complexed with the 8-mer nef peptide (VPLRPMTY) [23] which comes from a region conserved in the HIV-1 and HIV-2 genomes.…”

Section: Introductionmentioning

confidence: 99%

Production and crystallization of MHC class I B allele single peptide complexes

et al. 1996

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“…30 However, we are not aware of previous reports of gene-environment interactions affecting susceptibility to an infectious disease. HLA alleles have been associated with susceptibility to other infectious pathogens 13,14 including P. malariae, 31,32 M. tuberculosis [33][34][35] and HIV. [36][37][38][39][40][41] These associations are often attributed to changes in T-cell response caused by modified interaction between the variant HLA allele and antigenic peptides.…”

Section: Resultsmentioning

confidence: 99%