6ID4

Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01

Summary for 6ID4

• Entry DOI: 10.2210/pdb6id4/pdb
• Descriptor: MHC class I antigen, Beta-2-microglobulin, Heavy chain, ... (8 entities in total)
• Functional Keywords: immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 185292.42

Authors

Lescar, J.,Wong, Y.H.,Liew, C.W.,Gu, Y.,MacAry, P.A. (deposition date: 2018-09-08, release date: 2019-02-06, Last modification date: 2024-10-23)

Primary citation

Gu, Y.,Wong, Y.H.,Liew, C.W.,Chan, C.E.Z.,Murali, T.M.,Yap, J.,Too, C.T.,Purushotorman, K.,Hamidinia, M.,El Sahili, A.,Goh, A.T.H.,Teo, R.Z.C.,Wood, K.J.,Hanson, B.J.,Gascoigne, N.R.J.,Lescar, J.,Vathsala, A.,MacAry, P.A.
Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.
Nat Commun, 10:893-893, 2019

PubMed Abstract: Our understanding of the conformational and electrostatic determinants that underlie targeting of human leukocyte antigens (HLA) by anti-HLA alloantibodies is principally based upon in silico modelling. Here we provide a biochemical/biophysical and functional characterization of a human monoclonal alloantibody specific for a common HLA type, HLA-A*11:01. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*11:01 and compare the structural determinants with those utilized by T-cell receptor (TCR), killer-cell immunoglobulin-like receptor (KIR) and CD8 on the same molecule. These data provide a mechanistic insight into the paratope-epitope relationship between an alloantibody and its target HLA molecule in a biological context where other immune receptors are concomitantly engaged. This has important implications for our interpretation of serologic binding patterns of anti-HLA antibodies in sensitized individuals and thus, for the biology of human alloresponses.

PubMed: 30792391
DOI: 10.1038/s41467-019-08790-1

Experimental method

X-RAY DIFFRACTION (2.4 Å)