Back to Search
Start Over
Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.
- Source :
- Communications Biology; 3/28/2022, Vol. 5 Issue 1, p1-17, 17p
- Publication Year :
- 2022
-
Abstract
- 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<superscript>+</superscript> 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. The identification and structural analysis of HLA-E-VL9-targeting antibodies that block a natural killer (NK) cell receptor pathway and regulate NK function in vitro. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 23993642
- Volume :
- 5
- Issue :
- 1
- Database :
- Complementary Index
- Journal :
- Communications Biology
- Publication Type :
- Academic Journal
- Accession number :
- 156318428
- Full Text :
- https://doi.org/10.1038/s42003-022-03183-5