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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Detalles Bibliográficos
Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960791/
https://www.ncbi.nlm.nih.gov/pubmed/35347236
http://dx.doi.org/10.1038/s42003-022-03183-5
Descripción
Sumario: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.

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