8T6M

Human leukocyte antigen bound by two alloreactive antibody Fabs

Summary for 8T6M

• Entry DOI: 10.2210/pdb8t6m/pdb
• EMDB information: 41072
• Descriptor: JTK191b_M07_Light, JTK191b_M07_Fab, JTK191b_L02_Light, ... (7 entities in total)
• Functional Keywords: antibody, human leukocyte antigen, graft rejection, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 7
• Total formula weight: 128859.51

Authors

Kizziah, J.L.,Killian, J.T.,Diaz-Avalos, R.,Qiu, S.,Yang, G.,Green, T.,Lund, F.E. (deposition date: 2023-06-16, release date: 2024-12-25, Last modification date: 2026-01-14)

Primary citation

Killian Jr., J.T.,King, R.G.,Lucander, A.C.K.,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.,Good, D.B.,Kelso, S.,Houp, J.A.,Rosenblum, F.,Porrett, P.M.,Ong, S.C.,Kumar, V.,Saphire, E.O.,Kearney, J.F.,Randall, T.D.,Rosenberg, A.F.,Green, T.J.,Lund, F.E.
Topography of the HLA-A protein enforces shared and convergent immunodominant B cell and antibody alloresponses in transplant recipients.
Immunity, 58:3040-3060.e12, 2025

PubMed Abstract: Donor-specific antibody responses against human leukocyte antigen (HLA) proteins mismatched between transplant donors and recipients cause allograft loss, yet the structural HLA epitopes targeted by alloreactive B cells and antibodies remain largely unresolved. We profiled the HLA-A01:01-specific B cell response in the transplanted kidney and blood of a recipient undergoing antibody-mediated rejection and identified immunodominant B cell and antibody responses that emerged early in the alloimmune response. These responses were focused on topographically exposed mismatched HLA residues located in the α helices along the peptide-binding groove of HLA-A01:01. We demonstrated that the anti-HLA-A01:01 B cell alloresponse converged and was maintained on this same immunodominant HLA subregion, which comprises only 20% of the HLA molecule, in a diverse group of HLA-A01:01-mismatched transplant recipients. Thus, the B cell and antibody alloresponses appear tightly focused on a topographically defined region on the HLA-A01:01 crown that is conserved across individuals expressing distinct constellations of self-HLA-A.

PubMed: 41289995
DOI: 10.1016/j.immuni.2025.10.014

Experimental method

ELECTRON MICROSCOPY (3.14 Å)