Caracterización del complejo mayor de histocompatibilidad clase II en primates del género Aotus

Abstract

This work was aimed to contribute to increase our knowledge on the MHC class II in monkeys from the genus Aotus. Determining the sequences of MHC-DPA and MHC-DRA genes has allowed to complete the characterisation of the Aotus MHC, contributing towards validating the role of this primate as experimental model and increasing our knowledge regarding MHC gene evolution in primates. It also dealt with in–depth analysis of MHC-DR genes’ convergence and polymorphism in primates. The study involves computational modelling of MHC-peptide binding methodologies (based on quantum chemistry and neural networks) as necessary tools for understanding the mechanisms of MHC class II peptide presentation to T-lymphocytes. Studying peptide binding region polymorphism has enabled developing strategies (pocket profiles) for efficiently reducing the amount of systems to be considered when designing peptides to be used as candidates for an antimalarial vaccine. Data-mining regarding Ramachandran distribution led to developing an amino acid structural similarity scale for use in developing/designing peptides as vaccine candidates. It was found that protein secondary structure has a clear relationship with amino acid substitution and mutability evolutionary patterns. A conceptual framework thus emerged aimed at developing peptide-based vaccines as a basis for studying the mayor histocompatibility complex polymorphism, the physicochemical/structural restrictions shaping the molecular recognition involved in MHC-peptide interaction and using computational methodologies for quantifying MHC-peptide binding.