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Composition of immunoglobulin CDRs: geography and co-evolution with fever-inducing pathogens

Grant number: 20/06438-1
Support type:Regular Research Grants
Duration: December 01, 2020 - November 30, 2022
Field of knowledge:Biological Sciences - Immunology - Immunochemistry
Principal Investigator:Maristela Martins de Camargo
Grantee:Maristela Martins de Camargo
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:João Marcelo Pereira Alves ; Razvan Costin Stan

Abstract

Neutralization of a pathogen requires optimal affinity between the specific antibody and the pathogen. Such affinity is determined by the aminoacids landscape (charges and shapes) that form the contact regions. A pathogen can evade the host's immune system by changing its aminoacids, while the immunoglobulin repertoire of the host holds strategies for inducing high rates of mutation in its contact regions, the CDRs. Higher temperatures induced by fever during a pathology can change the conformation of those contact regions, improving or worsening the neutralizing characteristics of an antibody. In this project, we will evaluate the aminoacid composition of CDR regions of neutralizing antibodies against P. falciparum and SARS-CoV-2, aiming to clarify the contribution of the germline repertoire compared to the repertoire obtained after affinity maturation, which happens under influence of the pathogen. We will contrast germline repertoires of several modern populations, distributed in different geographic locations, with the repertoire from ancient populations (Neanderthals, Denisovans, etc). We anticipate that this project will contribute to the understanding of co-evolution of pathogens and immunoglobulins in two aspects: (i) the influence of geography and local diseases as selective pressures on immunoglobulin repertoire, and (ii) contribution of the potential for conformational changes held by neutralizing immunoglobulins under fever episodes, to the pathogenesis of malaria and COVID-19. (AU)