Alloreactivity and autoreactivity converge to support B cell epitope targeting in transplant rejection
Killian, J. T.; King, R. G.; Kizziah, J. L.; Fucile, C. F.; Diaz-Avalos, R.; Qiu, S.; Silva-Sanchez, A.; Mousseau, B. J.; Macon, K. J.; Callahan, A. R.; Yang, G.; Hossain, M. E.; Akther, J.; Houp, J. A.; Rosenblum, F. D.; Porrett, P. M.; Ong, S. C.; Kumar, V.; Mobley, J.; Saphire, E. O.; Kearney, J. F.; Randall, T. D.; Rosenberg, A. F.; Green, T. J.; Lund, F. E.
Show abstract
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.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause severe disease 96%
- Diverse priming outcomes under conditions of very rare precursor B cells 95%
- Self-reactive B cells traverse a perfect storm of somatic mutagenesis to cause a virus-induced autoimmune disease 95%
Similar papers in this journal
Similar papers in this journal
- Deep repertoire mining uncovers ultra-broad coronavirus neutralizing antibodies targeting multiple epitopes 96%
- Clonal Expansion and Diversification of Germinal Center and Memory B Cell Responses to Booster Immunization in Primates 95%
- Broadly-recognized, cross-reactive SARS-CoV-2 CD4 T cell epitopes are highly conserved across human coronaviruses and presented by common HLA alleles 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.