Nature communications · 2024
Viral sequence determines HLA-E-restricted T cell recognition of hepatitis B surface antigen.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Murugesan Gavuthami, Paterson Rachel L, Kulkarni Rakesh, Ilkow Veronica, Suckling Richard J, Connolly Mary M, Karuppiah Vijaykumar, Pengelly Robert, Jadhav Archana, Donoso Jose, Heunis Tiaan, Bunjobpol Wilawan, Philips Gwilym, Ololade Kafayat, Kay Daniel, Sarkar Anshuk, Barber Claire, Raj Ritu, Perot Carole, Grant Tressan, Treveil Agatha, Walker Andrew, Dembek Marcin, Gibbs-Howe Dawn, Hock Miriam, Carreira Ricardo J, Atkin Kate E, Dorrell Lucy, Knox Andrew, Leonard Sarah, Salio Mariolina, Godinho Luis F
Аннотация
The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env371-379, identified through bioinformatic predictions and verified by biochemical and cellular assays. Using a soluble affinity-enhanced T cell receptor (TCR) (a09b08)-anti-CD3 bispecific molecule to probe HLA-E presentation of the Env371-379 peptides, we demonstrate that only the most stable Env371-379 variant, L6I, elicits functional responses to a09b08-anti-CD3-redirected polyclonal T cells co-cultured with targets expressing endogenous HBsAg. Furthermore, HLA-E-Env371-379 L6I-specific CD8+ T cells are detectable in HBV-naïve donors and people with chronic HBV after in vitro priming. In conclusion, we provide evidence for HLA-E-mediated HBV Env peptide presentation, and highlight the effect of viral mutations on the stability and targetability of pHLA-E molecules.