| Autor: |
Killian JT, Glenn King R, Lucander ACK, Kizziah JL, Fucile CF, Diaz-Avalos R, Qiu S, Silva-Sanchez A, Mousseau BJ, Macon KJ, Callahan AR, Yang G, Emon Hossain M, Akther J, Good DB, Kelso S, Houp JA, Rosenblum F, Porrett PM, Ong SC, Kumar V, Saphire EO, Kearney JF, Randall TD, Rosenberg AF, Green TJ, Lund FE |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 24. Date of Electronic Publication: 2024 Jul 24. |
| DOI: |
10.1101/2023.03.31.534734 |
| Abstrakt: |
Donor-specific antibody (DSA) responses against human leukocyte antigen (HLA) proteins mismatched between kidney transplant donors and recipients cause allograft loss. The rules governing the immunogenicity of non-self donor HLA are poorly understood. Using single-cell, molecular, structural, and proteomic techniques, we profiled the HLA-specific B cell response in the kidney and blood of a transplant recipient with antibody-mediated rejection (AMR). We observed an immunodominant B cell antibody response focused on topographically exposed, solvent-accessible mismatched HLA residues along the peptide-binding groove - a subregion comprising only 20% of the HLA molecule. We further demonstrated that, even within a diverse cohort of transplant recipients, the B cell alloresponse consistently converges on this same immunodominant subregion on the crown of the HLA molecule. Based on these findings, we propose that B cell immunodominance in transplant rejection relies on antigenic topography, and we suggest that this link could be exploited for organ matching and therapeutics. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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