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RESEARCH PRODUCT

Role of HLA-B α-3 domain amino acid position 194 in HIV disease progression

Alfredo SalernoAlba GrifoniCarla MontesanoPaolo PalmaMassimo AmicosanteVittorio Colizzi

subject

Models MolecularGene ExpressionKIR3DS1HIV InfectionsPeptide bindingLeukocyte Immunoglobulin-like Receptor B1ModelsImmunologicReceptorsInnateReceptors ImmunologicChildReceptorGeneticschemistry.chemical_classificationCross Infectioneducation.field_of_studyReceptors KIR3DL1Polymorphism Genetic; Models Molecular; Humans; Disease Progression; Gene Expression; HLA-B Antigens; Immunity Innate; Child; Receptors KIR3DL1; Protein Binding; HIV-1; Binding Sites; Receptors KIR3DS1; Receptors Immunologic; HIV Infections; Antigens CD; Protein Structure Tertiary; Signal Transduction; Amino Acid Substitution; Cross InfectionHLA-BCDAmino acidDisease ProgressionKIR3DL1Protein BindingSignal TransductionReceptors KIR3DS1Protein StructureImmunologyPopulationHuman leukocyte antigenBiologyGeneticKIR3DL1Antigens CDHumansPolymorphismAntigenseducationMolecular BiologySettore MED/04 - Patologia GeneralePolymorphism GeneticBinding SitesInnate immune systemImmunityMolecularImmunity InnateProtein Structure TertiaryAmino Acid SubstitutionchemistryHLA-B AntigensImmunologyHIV-1Tertiary

description

HLA class I molecules play a role in the regulation of innate immune response. Therefore, the interaction of HLA class I molecules with different activating and inhibitory receptors leads to balancing the immune response. Among the different family of receptors, NK receptors KIR3DL1/S1 and LIR1, play a major role. Aim of this study was to evaluate the role of amino acid polymorphic positions of HLA class I molecules interacting with NK receptors in HIV progression. In order to minimize the influence of viral variability, a cohort of children with a nosocomial monophyletic HIV-1 infection from the Benghazi Children Hospital has been evaluated. To assess the role of single amino acid positions, we translated all HLA alleles in the different amino acid position polymorphisms. Interestingly, the polymorphism Val 194 located in the α3-domain of HLA-B, resulted associated with LTNP (LTNP=73.08%, FP=34.78%; P<0.02). When Val is present at position 194, HLA-B is known to interact with the receptor LIR1 (ILT2/LILRB1/CD85j). Therefore, we analyzed the role of the polymorphism in position 194 in HLA-B/LIR1 interaction by homology molecular modeling. The change Val to Ile at position 194 alters significantly the network of interaction between the amino acid residues of HLA-B and LIR1. In conclusion, considering the limitation of the small population evaluated, polymorphisms outside the peptide binding region of the HLA class I molecule can play a key role in HIV progression through interaction with other immune-relevant receptors.

yearjournalcountryeditionlanguage
2013-04-01Molecular Immunology
https://doi.org/10.1016/j.molimm.2012.09.009