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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Vydáno v:	Communications biology Ročník 5; číslo 1; s. 271 - 17
Hlavní autoři:	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.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 28.03.2022 Nature Publishing Group Nature Portfolio
Témata:	13/1 13/106 13/109 13/31 14/28 14/34 14/63 38 38/77 42 631/250/1619/382 631/250/2152/2153/1291 631/535/1266 631/61/51/1568 64/60 82 82/80 82/83 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
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Popis
Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2399-3642 2399-3642
DOI:	10.1038/s42003-022-03183-5