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

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 isolati...

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Bibliographic Details
Published in:Communications biology Vol. 5; no. 1; pp. 271 - 17
Main Authors: Li, Dapeng, Brackenridge, Simon, Walters, Lucy C., Swanson, Olivia, Harlos, Karl, Rozbesky, Daniel, Cain, Derek W., Wiehe, Kevin, Scearce, Richard M., Barr, Maggie, Mu, Zekun, Parks, Robert, Quastel, Max, Edwards, Robert J., Wang, Yunfei, Rountree, Wes, Saunders, Kevin O., Ferrari, Guido, Borrow, Persephone, Jones, E. Yvonne, Alam, S. Munir, Azoitei, Mihai L., Gillespie, Geraldine M., McMichael, Andrew J., Haynes, Barton F.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 28.03.2022
Nature Publishing Group
Nature Portfolio
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Animals
Antibodies
Biology
Biomedical and Life Sciences
Cytomegalovirus
Cytotoxicity
Cytotoxicity, Immunologic
Histocompatibility antigen HLA
Histocompatibility Antigens Class I - genetics
HLA Antigens
HLA-E Antigens
Humans
Immunoglobulin G
Immunoglobulin M
Immunoglobulins - metabolism
Killer Cells, Natural
Life Sciences
Lymphocytes B
Mice
Natural killer cells
NKG2 antigen
Peptides - metabolism
Protein Sorting Signals
ISSN:2399-3642, 2399-3642
Online Access:Get full text
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Summary: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. 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.
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ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-022-03183-5