Estudo da interação de peptídeos do citomegalovírus humano a diferentes especificidades HLA de classe I: Uma abordagem in silico

• Ano de defesa: 2018
• Autor(a) principal: Stephanie Santos de Almeida
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; MEDICINA - FACULDADE DE MEDICINA; Programa de Pós-Graduação em Ciências Aplicadas à Cirurgia e à Oftalmologia; UFMG
• Palavras-chave em Português: Citomegalovirus; Proteínas Virais; Antígenos HLA; Herpesviridae; Linfócitos T; Transplante
• Link de acesso: http://hdl.handle.net/1843/43301

Cytomegalovirus (HCMV) is a common human herpesvirus mostly asymptomatic in immunocompetent population. In immunosuppression, as transplantation, HCMV can reactive and affect transplant outcome, causing changes in clinical status. HLA is an important system that participates in antigen presentation and T cell activation, which imposes important barrier to transplantation. Matches between HLA guides donor-receptor compatibility. We asked if different HLA would be associated with resistance to HCMV. We chose 10 most immunogenic HCMV proteins related to CD8+ response. The proteins sequence was taken from UniProt Database and immunogenic peptides for MHC-I were predicted by T Cell Epitopes MHC binding Prediction using Artificial Neural Networks to calculate predicted Ic50 at Immune Epitope Database website against 27 types of I HLAs. The peptides affinities were classified by Ic50 into high (<50 nM), medium (50-500 nM) and low (>500 nM). The majority of predicted peptides (98.30%, varying 82.3% to 99.7% for the 10 proteins) were low affinity with little chance to interact with HLAs. On average, 0.41 peptides show high affinity Ic50 in the HLA. When classified by the number of immunogenic peptides (Ic50 below 500 nM), UL48 (biggest) were found to be the most immunogenic followed by UL55, UL29, UL32, UL28, Pp65 (most studied), UL122, UL123, US3, US32. These analyses revealed that some HLA are optimal to present HCMV epitopes, as A*02:03, A*02:06, A*31:01, A*68:01; while others are poor presenters as A*01:01, A*26:01, B*51:01, B*44:02. HLA A*02:03 was the best HLA to respond against HCMV peptides displaying high levels of interaction with all protein peptides but US32. In contrast HLA A*26:01, A*01:01, B*51:01 were the worst HLAs to presents HCMV peptides displaying none or just few interactions with predicted peptides from all proteins. Clinical context, knowing the interaction between the HLAs and HCMV proteins might help infer the risk of virus infection on post transplantation.