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Worldwide HLA-E nucleotide and haplotype variability reveals a conserved gene for coding and 3′ untranslated regions

Authors

  • L. P. Felício,

    1. Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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  • I. O. P. Porto,

    1. Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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  • C. T. Mendes-Junior,

    1. Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil
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  • L. C. Veiga-Castelli,

    1. Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
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  • K. E. Santos,

    1. Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás, Brazil
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  • R. P. Vianello-Brondani,

    1. Laboratório de Biotecnologia, EMBRAPA Arroz e Feijão, Santo Antônio de Goiás, Goiás, Brazil
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  • A. Sabbagh,

    1. Institut de Recherche pour le Développement, UMR 216 Mère et enfant face aux infections tropicales, Paris, France
    2. Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, France
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  • P. Moreau,

    1. CEA, Institut des Maladies Emergents et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis, Paris, France
    2. Université Paris-Diderot, Sorbonne Paris – Cité, UMR E5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis, Paris, France
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  • E. A. Donadi,

    1. Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
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  • E. C. Castelli

    Corresponding author
    1. Department of Pathology, School of Medicine of Botucatu, UNESP – Univ Estadual Paulista, Botucatu, São Paulo, Brazil
    • Correspondence

      Erick C. Castelli

      Departamento de Patologia

      Faculdade de Medicina de Botucatu

      UNESP – Universidade Estadual Paulista

      Botucatu 18618-970

      Sao Paulo

      Brazil

      Tel: +55 14 3880 1696

      Fax: +55 14 3815 2348

      e-mail: castelli@fmb.unesp.br

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Abstract

The human leukocyte antigen-E (HLA-E) locus is a human major histocompatibility complex (MHC) gene associated with immune-modulation and suppression of the immune response by the interaction with specific natural killer (NK) and T cell receptors (TCRs). It is considered one of the most conserved genes of the human MHC; however, this low nucleotide variability seems to be a consequence of the scarce number of studies focusing on this subject. In this manuscript we assessed the nucleotide variability at the HLA-E coding and 3′ untranslated regions (3′UTRs) in Brazil and in the populations from the 1000Genomes Consortium. Twenty-eight variable sites arranged into 33 haplotypes were detected and most of these haplotypes (98.2%) are encoding one of the two HLA-E molecules found worldwide, E*01:01 and E*01:03. Moreover, three worldwide spread haplotypes, associated with the coding alleles E*01:01:01, E*01:03:01 and E*01:03:02, account for 85% of all HLA-E haplotypes, suggesting that they arose early before human speciation. In addition, the low nucleotide diversity found for the HLA-E coding and 3′UTR in worldwide populations suggests that the HLA-E gene is in fact a conserved gene, which might be a consequence of its key role in the modulation of the immune system.

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