Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA324605 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4061820_1.fastq.gz | Fastqsanger.gz | |||
| SRR4061820_2.fastq.gz | Fastqsanger.gz | |||
| SRR4061830_1.fastq.gz | Fastqsanger.gz | |||
| SRR4061830_2.fastq.gz | Fastqsanger.gz | |||
| SRR4061840_1.fastq.gz | Fastqsanger.gz |
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Project description:Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. Using single cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific (alloreactive) B cell response in kidney and blood of a transplant recipient with antibody-mediated rejection (AMR). We identified 14 distinct alloreactive B cell lineages, which spanned the rejected organ and blood and expressed high-affinity anti-donor HLA-specific B cell receptors – many of which were clonally linked to circulating DSA. The alloreactive B cell response was focused on exposed, solvent-accessible mismatched HLA residues, while also demonstrating extensive contacts with self-HLA residues. Consistent with structural evidence of self-recognition, measurable autoreactivity by donor-specific B cells was common and positively correlated with anti-donor affinity maturation. Thus, allo- and self-reactive signatures appeared to converge, suggesting that during AMR, the recognition of non-self and breaches of tolerance conspire to produce a pathogenic donor-specific adaptive response.
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Project description:Immune profiles were performed retrospectively in highly sensitized kidney transplant candidates Our hypothesis was that baseline differences in immune profiles could help identify candidates that respond to desensitization therapy. Single-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in 20 highly sensitized kidney transplant candidates undergoing desensitization therapy.
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