Defining the structural basis for human alloantibody binding to human leukocyte antigen allele HLA-A*11:01.
Nat Commun
; 10(1): 893, 2019 02 21.
Article
em En
| MEDLINE
| ID: mdl-30792391
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*1101. We present a 2.4 Å resolution map of the binding interface of this antibody on HLA-A*1101 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígeno HLA-A11
/
Isoanticorpos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article