Rapid Communication HLA-E polymorphisms in an Afro-descendant Southern Brazilian population Luana Carvalho dos Santos, Luciane Viater Tureck, Pryscilla Fanini Wowk, Sibelle Botogosque Mattar, Georgia Fernanda Gelmini, João Carlos Marques Magalhães, Maria da Graça Bicalho, Valéria Maria Munhoz Sperandio Roxo ⇑ Laboratory of Immunogenetics and Histocompatibility, Genetics Department, Universidade Federal do Paraná, Curitiba, Brazil article info Article history: Received 25 April 2012 Accepted 26 October 2012 Available online 5 November 2012 abstract HLA-E is a non-classical I (Ib) gene which has limited polymorphism and low levels of tissue expression. Currently, 11 alleles are described in the literature with only three protein products. In the present study we investigated HLA-E gene variations at exons 2 and 3 and calculated allele, genotype and haplotype fre- quencies in a sample of 152 individuals who reported themselves as being Afro-descendants and who are voluntary bone marrow donors living in the state of Paraná, Brazil. The most frequent allele in the sample analyzed was the E / 01:01 (59.21%). The presence of the E / 01:04 allele was not detected suggesting that it has a very low worldwide frequency or that this allele may be an artifact of sequencing. We reported the most frequent alleles found as well as genotypes and haplotypes and compared our results with the few other studies found in the literature. This study is the first to investigate Afro-descendants from the South of Brazil. Ó 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction The three non-classical class Ib genes, HLA-E, HLA-F and HLA-G, located in the class I region of the Major Histocompatibility Complex (MHC 1 ) in humans can be distinguished from the classical class Ia genes by their low allelic polymorphism, specific expres- sion patterns, peptide binding properties and immune-related functions [1]. The recent description of HLA-E and HLA-G antigens as ligands for distinct killing inhibitory receptors expressed by immunocompetent cells has highlighted the specific role of non- classical class I molecules in modulating immune responses. In contrast to HLA-G, which has a restricted pattern of expression [2], HLA-E is ubiquitously expressed [3]. HLA-E is located between the HLA-C and -A genes [4] and, unlike MHC class Ia, is highly conserved and the biological significance of its genetic polymorphism is uncertain [5]. Currently, 11 alleles are described in the literature: HLA-E (E / 01:01:01:01, E / 01:01:01:02, E / 01:01:01:03, E / 01:03:01:01, E / 01:03:01:02, E / 01:03:02:01, E / 01:03:02:02, E / 01:03:03, E / 01:03:04, E / 01:03:05, E / 01:04), which encode only three protein products (IMGT/HLA Database) [6]. There are three allelic variations which are non-synonymous and corre- spond to E / 01:01, E / 01:03 and E / 01:04 [7]. Alleles HLA-E / 01:01 and HLA-E / 01:03 differ only at codon 107 of exon 3; HLA-EG presents codon (GGG) which stands for asparagine whereas HLA-ER has an arginine (AGG) [8]. These two alleles seem to have different levels of expression and HLA-EG molecules are found in a higher concen- tration in the cell surface as compared to HLA-ER [9]. This difference in expression of the two alleles not only reflects the affinity of HLA- E107G for peptides but also the greater stability of the complex on the cell surface. The variation E / 01:04 has two nucleotide substitu- tions; the first is located at codon 107 which encodes a glycine (GGG) instead of an arginine (AGG). The second at codon 157 which presents a substitution of an arginine for a glycine, differentiates these alleles from the afore mentioned. The HLA-E molecule shows less variation in its amino acid se- quence than other HLA class I molecules [10]. For the stabilization of the molecule on the cell surface, peptides derived from the leader sequence of several HLA class I molecules including HLA- A, HLA-B, HLA-C and HLA-G are requested [11]. Evidences suggest that HLA-E molecules can also bind to viral and bacterial peptides [12]. HLA-E has been identified as a ligand for the CD94/NKG2A and CD94/NKG2C receptors expressed in NK cells, which are part of innate immunity [13]. This interaction is dependent on the association of HLA-E with nonamers derived from class I leader peptides and variations in these peptides affect the stability of HLA-E determining whether HLA-E/peptide complexes are stable and can be expressed in the cell surface and can protect this cell 0198-8859/$36.00 - see front matter Ó 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.humimm.2012.10.020 ⇑ Corresponding author. Address: Laboratório de Imunogenética e Histocompa- tibilidade, Departamento de Genética, Universidade Federal do Paraná, R. Cel. Francisco H. dos Santos S/N, Centro Politécnico – Jardim das Américas, CP 19071, CEP 81.530.990, Curitiba, PR, Brazil. Fax: +55 41 3266 2042. E-mail address: valroxo@ufpr.br (V.M.M.S. Roxo). 1 Abbreviations: ADP, Afro-descendants – Paraná; AEUA, African American-United States; AMOVA, analysis of molecular variance; BRA, Brazilians – São Paulo; CAD, cau- casians – Denmark; MHC, major histocompatibility complex; SNP, single nucleotide polymorphism. Human Immunology 74 (2013) 199–202 Contents lists available at SciVerse ScienceDirect www.ashi-hla.org journal homepage: www.elsevier.com/locate/humimm