Biology subjects

Pati, N. B.

Publications and source records attributed to Pati, N. B..

2 recordsLinked to original sources

bioRxiv2025

Ultra long-lived plasma cells in the human small intestine produce microbiota-reactive IgA antibodies

A large fraction of the intestinal microbiota is highly coated with secretory IgA, and bacteria-specific IgA is believed to shape the composition of the microbiota. A hallmark of the adaptive immune system is immunological memory to specific antigens. However, whether there is strong and persistent memory of secretory antibodies to bacterial antigens has not been determined. Here we show that ultra long-lived CD19- CD45- (age>20 years) plasma cells (PCs) residing in the human small intestine produce IgA that binds to most taxa of a diverse anaerobic microbiota culture. Long-lived CD19-CD45+ (age>10 years) and short-lived CD19+CD45+ (age<2 years) PCs also produced IgA with broad bacterial reactivity. A clear correlation between high-binding and low-binding taxa was observed across the PC subsets. We also found that host PCs were depleted in acute intestinal graft versus host disease, a condition strongly associated with loss of microbiota diversity. Together, we show that bacterial antigens in the intestine induce an extremely stable, long-lasting humoral immune memory that may be important for the long-term stability and resilience of the intestinal microbiome.

immunology↗

bioRxiv2020

Invariant chain with an AP3 interacting sorting signal is sorted to late endosomal compartments and may improve MHC class I loading and presentation.

Invariant chain (Ii) is traditionally known as the dedicated MHCII chaperone. Recent reports have broadened our understanding about various tasks that Ii plays including its physiological role in MHCI cross-presentation. Ii bound MHCI via the MHCII scaffolding CLIP peptide may facilitate MHCI trafficking to the endosomal pathway. The sorting function of Ii depends on two leucine-based sorting signals present in the cytoplasmic tail that acts as binding sites for the adaptor proteins AP-1/AP-2. Here we increased the Ii cross-presentation potency by replacing these with an AP3 motif resulting an efficient transport of Ii from TGN to late endosomes. We also replaced the CLIP region of li with a therapeutically relevant peptide, MART-1. We found the Ii AP3mutant-MART1 construct was capable of loading MHCI and stimulate specific T-cell response more efficiently than the wild type counterpart. The results show that Ii with an AP3 binding sorting motif carrying peptide epitope(s) can promote efficient antigen presentation to cytotoxic T cells (CTLs) independent of the ER located classical MHCI peptide loading machinery.

immunology↗