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...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Springer Nature
2022
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| _version_ | 1797106974046814208 |
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| author | Li, D Brackenridge, S Walters, L Harlos, K Rozbesky, D Quastel, M Borrow, P Jones, EY Gillespie, G McMichael, A |
| author_facet | Li, D Brackenridge, S Walters, L Harlos, K Rozbesky, D Quastel, M Borrow, P Jones, EY Gillespie, G McMichael, A |
| author_sort | Li, D |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T07:08:33Z |
| format | Journal article |
| id | oxford-uuid:f1d29120-a307-4036-a147-673b04384f10 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:08:33Z |
| publishDate | 2022 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:f1d29120-a307-4036-a147-673b04384f102022-05-24T14:22:00ZMouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f1d29120-a307-4036-a147-673b04384f10EnglishSymplectic ElementsSpringer Nature2022Li, DBrackenridge, SWalters, LHarlos, KRozbesky, DQuastel, MBorrow, PJones, EYGillespie, GMcMichael, AThe 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. |
| spellingShingle | Li, D Brackenridge, S Walters, L Harlos, K Rozbesky, D Quastel, M Borrow, P Jones, EY Gillespie, G McMichael, A Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title | Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title_full | Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title_fullStr | Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title_full_unstemmed | Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title_short | Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity |
| title_sort | mouse and human antibodies bind hla e leader peptide complexes and enhance nk cell cytotoxicity |
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