The molecular basis of how buried human leukocyte antigen polymorphism modulates natural killer cell function.
Proc Natl Acad Sci U S A
; 117(21): 11636-11647, 2020 05 26.
Article
en En
| MEDLINE
| ID: mdl-32404419
ABSTRACT
Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*5701 and HLA-B*5703 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*5701 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*5701, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*5701, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*5703, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Células Asesinas Naturales
/
Antígenos de Histocompatibilidad Clase I
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia