No association of TAP and LMP genetic polymorphism in human brucellosis and its complications M.J. Bravo a,b, *, J.D. Colmenero c , M.I. Queipo-OrtuÒo d,b , J. MartÎn e , R. Lavado a,b , A. Alonso a , A. Caballero a a Immunology Service, Carlos Haya University Hospital, Malaga, Spain b Imabis Foundation, Malaga, Spain c Infectious Diseases Service, Carlos Haya University Hospital, Malaga, Spain d Biochemistry and Molecular Biology Department, Faculty of Medicine, University of Malaga, Spain e Lopez-Neyra Institute of Biomedicine and Parasitology, Consejo Superior Investigaciones Cientìficas, Granada, Spain ARTICLE INFO Article history: Received 15 December 2009 Accepted 5 May 2010 Available online 12 May 2010 Keywords: TAP LMP Polymorphism Human Brucellosis ABSTRACT Molecules involved in antigen processing (LMP) and peptide transport (TAP) are coded by polymorphic genes. This polymorphism may influence the peptide antigen selection process and play a role in the pathogenesis of human brucellosis. We studied the polymorphism of the antigen processing and transport genes (LMP and TAP) in 61 patients with human brucellosis and 102 controls from southern Spain. We found no differences in the frequencies of the LMP and TAP genotypes between the patients and the controls. Study of the patients with and without focal or complicated forms showed a significant increase in the TAP2A/TAP2F genotype in those with focal forms compared with those without focal forms (16% vs 0%, p = 0.02), though this difference lost its significance after correction for the number of comparisons. This study suggests that larger studies will be needed to confirm or rule out the possible association of the TAP2A/TAP2F genotype or other possible associations with focal forms of brucellosis.  2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. 1. Introduction Brucellosis is a zoonosis caused by a bacteria of the genus Bru- cella. The disease affects human beings in areas where it remains endemic, especially in countries around the Mediterranean basin, and in the Middle East, India, and South and Central America [1,2]. Although the incidence of human brucellosis has decreased in Spain over the last two decades, it nevertheless remains relatively high in comparison with other European countries, with 0.38 cases per 100,000 inhabitants and up to 0.66 cases per 100,000 inhabit- ants in Andalusia, southern Spain [3]. The disease frequently pre- sents with an extended clinical course and is associated with high rates of therapeutic failure, relapse, and complications [4]. The cellular immune responses represent a critical part of the host defense against intracellular bacterial infections. Immunity against Brucella depends crucially on specific antigen T cells that mediate the activation of macrophages, which are the greatest effectors in the elimination of this intracellular pathogen. Bacterial protein antigens are presented to the cooperating T cells with a CD4 + phenotype. However, some Brucella antigens are expressed in the context of the major histocompatibility complex (MHC) class I, which results in the activation of cytotoxic T cells with a CD8 + phenotype. Studies in rats and cell cultures have shown that CD8 + cells participate actively in the protective immunity against brucel- losis [5]. Antigen presentation is essentially dependent on the protea- some, an intracellular complex of proteases entrusted with the degradation of proteins to peptides for their presentation as anti- gens. The proteasomes play a secondary but nevertheless crucial role in the functioning of the adaptative immune system. The anti- gen peptides are presented by the proteins of the MHC class I on the surface of antigen presenting cells (APC). These peptides are prod- ucts of the proteasome degradation of proteins derived from the invasive pathogen. Although the common proteasomes can partic- ipate in this process, a specialized complex, composed of proteins the expression of which is induced by interferon-, is involved in producing peptides with the optimal composition and size for MHC class I binding; this complex is called the immunoproteasome and is partially formed by subunits coded by the LMP2 and LMP7 genes [6]. Although the proteasome is the major proteolytic system pro- ducing antigen peptides, evidence suggests that other protease systems contribute to the production of the peptide pool. In addi- tion, studies have found that LMP2 and LMP7 are not required for efficient antigen presentation, suggesting that this protein plays a more specialized role in the production of class I associated pep- tides [7]. Only about 10% of the proteasome product has an ade- quate length; of the rest, 15–25% are extended precursors that * Corresponding author. E-mail address: mariajose.bravo@fundacionimabis.org (M.J. Bravo). Human Immunology 71 (2010) 708 –711 Contents lists available at ScienceDirect 0198-8859/10/$32.00 - see front matter  2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.humimm.2010.05.004