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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\u2009\u00c5 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.","bibjson":{"author":[{"initials":"Y","lastname":"Gu","name":"Gu Y"},{"initials":"YH","lastname":"Wong","name":"Wong YH"},{"initials":"CW","lastname":"Liew","name":"Liew CW"},{"initials":"CEZ","lastname":"Chan","name":"Chan CEZ"},{"initials":"TM","lastname":"Murali","name":"Murali TM"},{"initials":"J","lastname":"Yap","name":"Yap J"},{"initials":"CT","lastname":"Too","name":"Too CT"},{"initials":"K","lastname":"Purushotorman","name":"Purushotorman K"},{"initials":"M","lastname":"Hamidinia","name":"Hamidinia M"},{"initials":"A","lastname":"El Sahili","name":"El Sahili A"},{"initials":"ATH","lastname":"Goh","name":"Goh ATH"},{"initials":"RZC","lastname":"Teo","name":"Teo RZC"},{"initials":"KJ","lastname":"Wood","name":"Wood KJ"},{"initials":"BJ","lastname":"Hanson","name":"Hanson BJ"},{"initials":"NRJ","lastname":"Gascoigne","name":"Gascoigne NRJ"},{"initials":"J","lastname":"Lescar","name":"Lescar J"},{"initials":"A","lastname":"Vathsala","name":"Vathsala A"},{"initials":"PA","lastname":"MacAry","name":"MacAry PA"}],"identifier":[{"id":"10.1038/s41467-019-08790-1","type":"doi"},{"id":"30792391","type":"pubmed"}],"issue":["1"],"journal":{"iso_abbreviation":"Nat Commun","name":""},"pages":["893"],"title":"Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.","type":"article","url":"http://www.nature.com/articles/s41467-019-08790-1","volume":["10"],"year":[2019]},"in_pmc":"N","in_pmce":"Y","open_access":"Y"},"resolution":"2.40","same_as":{"pdbe":{"url":"https://www.ebi.ac.uk/pdbe/entry/pdb/6id4"},"rcsb":{"url":"https://www.rcsb.org/structure/6id4"}},"species":{"common_name":"Human","match_type":"histo:assign_species","scientific_name":"Homo sapiens","slug":"homo_sapiens"},"tcr":null,"title":"HLA-A*11:01 binding \"AIFQSSMTK\" with antibody at 2.40&#8491; resolution","unique_chain_count":5}}
