Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.

Journal Article (Journal Article)

The non-classical class Ib molecule human leukocyte antigen E (HLA-E) has limited polymorphism and can bind HLA class Ia leader peptides (VL9). HLA-E-VL9 complexes interact with the natural killer (NK) cell receptors NKG2A-C/CD94 and regulate NK cell-mediated cytotoxicity. Here we report the isolation of 3H4, a murine HLA-E-VL9-specific IgM antibody that enhances killing of HLA-E-VL9-expressing cells by an NKG2A+ NK cell line. Structural analysis reveal that 3H4 acts by preventing CD94/NKG2A docking on HLA-E-VL9. Upon in vitro maturation, an affinity-optimized IgG form of 3H4 showes enhanced NK killing of HLA-E-VL9-expressing cells. HLA-E-VL9-specific IgM antibodies similar in function to 3H4 are also isolated from naïve B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naïve B cell antibody pool have the capacity to enhance NK cell cytotoxicity.

Full Text

Duke Authors

Cited Authors

  • Li, D; Brackenridge, S; Walters, LC; Swanson, O; Harlos, K; Rozbesky, D; Cain, DW; Wiehe, K; Scearce, RM; Barr, M; Mu, Z; Parks, R; Quastel, M; Edwards, RJ; Wang, Y; Rountree, W; Saunders, KO; Ferrari, G; Borrow, P; Jones, EY; Alam, SM; Azoitei, ML; Gillespie, GM; McMichael, AJ; Haynes, BF

Published Date

  • March 28, 2022

Published In

Volume / Issue

  • 5 / 1

Start / End Page

  • 271 -

PubMed ID

  • 35347236

Pubmed Central ID

  • PMC8960791

Electronic International Standard Serial Number (EISSN)

  • 2399-3642

Digital Object Identifier (DOI)

  • 10.1038/s42003-022-03183-5

Language

  • eng

Conference Location

  • England