Avid binding by B cells to the Plasmodium circumsporozoite protein repeat suppresses responses to protective subdominant epitopes

Autor: Deepyan Chatterjee, Fiona J. Lewis, Henry J. Sutton, Joe A. Kaczmarski, Xin Gao, Yeping Cai, Hayley A. McNamara, Colin J. Jackson, Ian A. Cockburn
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports, Vol 35, Iss 2, Pp 108996- (2021)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.108996
Popis: Summary: Antibodies targeting the NANP/NVDP repeat domain of the Plasmodium falciparum circumsporozoite protein (CSPRepeat) can protect against malaria. However, it has also been suggested that the CSPRepeat is a decoy that prevents the immune system from mounting responses against other domains of CSP. Here, we show that, following parasite immunization, B cell responses to the CSPRepeat are immunodominant over responses to other CSP domains despite the presence of similar numbers of naive B cells able to bind these regions. We find that this immunodominance is driven by avid binding of the CSPRepeat to cognate B cells that are able to expand at the expense of B cells with other specificities. We further show that mice immunized with repeat-truncated CSP molecules develop responses to subdominant epitopes and are protected against malaria. These data demonstrate that the CSPRepeat functions as a decoy, but truncated CSP molecules may be an approach for malaria vaccination.
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