Banca de QUALIFICAÇÃO: HELMUT KENNEDY AZEVEDO DO PATROCINIO

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : HELMUT KENNEDY AZEVEDO DO PATROCINIO
DATE: 06/03/2023
TIME: 15:00
LOCAL: Auditório BioME
TITLE:

In silico investigation of nervous system protein peptides as candidates for molecular mimicry in Guillain-Barré syndrome and multiple sclerosis triggered by the Epstein-Barr virus

KEY WORDS:

GBS. MS. Molecular Mimicry. Cross-reactivity. pMHC-TCR interaction.

PAGES: 68
BIG AREA: Ciências Biológicas
AREA: Biologia Geral
SUMMARY:

Guillain-Barré Syndrome (GBS) and multiple sclerosis are autoimmune diseases associated with an immune response against peripheral (PNS) and central nervous system (CNS) autoantigens, respectively. Most studies on GBS immunopathology investigate the cross-reactivity between myelin sheath ganglioside antigens and carbohydrates from Campylobacter jejuni bacteria. However, GBS has a spectrum of subtypes and, particularly, the Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP) form has little evidence of a relationship with C. jejuni or of autoimmunity against gangliosides. The immunopathology of multiple sclerosis is better understood, with several protein autoantigens reported in the literature. In the present work, we screened the databases “The Human Protein Atlas,” AFND, and IEDB to select abundant proteins from the human nervous system (HNS), immunogenic proteins of the Epstein-Barr virus, and HLA haplotypes, respectively. Then we constructed a pipeline with several open-source computational tools to predict HLA binding to peptides and cytokine production. The following analysis used ten proteins from the HNS and 28 from EBV to predict the binding peptides of 21 common HLAs in the world population. From the search for haplotypes in the AFND, we found 1359 registered haplotypes distributed among 51 pairs of HLAs. After that, our pipeline compared nonapeptide anchors of EBV and myelin proteins for identity at critical residues for interaction with the T-cell receptor (TCR), establishing three selection criteria according to the relevance of each contact for TCR-peptide-MHC interaction. According to these criteria, all nervous system proteins presented peptides with relevant identity with EBV peptides. The prediction of IL-4 or IFN-γ cytokine stimulation allowed the discovery of which pairs of similar nonamers can induce the activation of Th1 or Th2 cells and perhaps cause autoimmunity through molecular mimicry. Seven proteins (APLP1, CNP, GlialCam, MAG, MBP, Periaxin, and PLP) presented pairs of similar peptide stimulators of cytokines IL-4, IFN-γ, or both. The P0 protein also presented pairs capable of inducing IL-4 or IFN-γ, though restricted to one or few HLAs or haplotypes. Given the high number of possible peptides that can cause molecular mimicry, our results align with the hypothesis that multiple antigens can cause immunity in multiple sclerosis and GBS. The nonamer pairs found here support further experimental investigations of these autoantigens and contribute to a better understanding of both pathologies.

COMMITTEE MEMBERS:
Presidente - 1267860 - GUSTAVO ANTONIO DE SOUZA
Externo ao Programa - 2985070 - JONAS IVAN NOBRE OLIVEIRA - nullInterno - 1507794 - RODRIGO JULIANI SIQUEIRA DALMOLIN