Scholars@Duke

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

Publication ,  Journal Article
Li, D; Brackenridge, S; Walters, LC; Swanson, O; Harlos, K; Rozbesky, D; Cain, DW; Wiehe, K; Scearce, RM; Barr, M; Mu, Z; Parks, R; Wang, Y ...
Published in: Commun Biol
March 28, 2022
Published version (DOI) Link to item

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.

Duke Scholars

S. Munir Alam
Author S. Munir Alam Medicine, Duke Human Vaccine Institute
Derek Wilson Cain
Author Derek Wilson Cain Medicine, Duke Human Vaccine Institute
Kevin J Wiehe
Author Kevin J Wiehe Medicine, Duke Human Vaccine Institute
Kevin O'Neil Saunders
Author Kevin O'Neil Saunders Surgery, Surgical Sciences
Guido Ferrari
Author Guido Ferrari Surgery, Surgical Sciences
Barton Ford Haynes
Author Barton Ford Haynes Medicine, Duke Human Vaccine Institute
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Published In

Commun Biol

DOI

10.1038/s42003-022-03183-5

EISSN

2399-3642

Publication Date

March 28, 2022

Volume

5

Issue

1

Start / End Page

271

Location

England

Related Subject Headings

  • Protein Sorting Signals
  • Peptides
  • Mice
  • Killer Cells, Natural
  • Immunoglobulins
  • Humans
  • Histocompatibility Antigens Class I
  • HLA-E Antigens
  • HLA Antigens
  • Cytotoxicity, Immunologic
 

Citation

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ICMJE
MLA
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Li, D., Brackenridge, S., Walters, L. C., Swanson, O., Harlos, K., Rozbesky, D., … Haynes, B. F. (2022). Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity. Commun Biol, 5(1), 271. https://doi.org/10.1038/s42003-022-03183-5
Li, Dapeng, Simon Brackenridge, Lucy C. Walters, Olivia Swanson, Karl Harlos, Daniel Rozbesky, Derek W. Cain, et al. “Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.” Commun Biol 5, no. 1 (March 28, 2022): 271. https://doi.org/10.1038/s42003-022-03183-5.
Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, et al. Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity. Commun Biol. 2022 Mar 28;5(1):271.
Li, Dapeng, et al. “Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.” Commun Biol, vol. 5, no. 1, Mar. 2022, p. 271. Pubmed, doi:10.1038/s42003-022-03183-5.
Li D, Brackenridge S, Walters LC, Swanson O, Harlos K, Rozbesky D, Cain DW, Wiehe K, Scearce RM, Barr M, Mu Z, Parks R, Quastel M, Edwards RJ, Wang Y, Rountree W, Saunders KO, Ferrari G, Borrow P, Jones EY, Alam SM, Azoitei ML, Gillespie GM, McMichael AJ, Haynes BF. Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity. Commun Biol. 2022 Mar 28;5(1):271.

Published In

Commun Biol

DOI

10.1038/s42003-022-03183-5

EISSN

2399-3642

Publication Date

March 28, 2022

Volume

5

Issue

1

Start / End Page

271

Location

England

Related Subject Headings

  • Protein Sorting Signals
  • Peptides
  • Mice
  • Killer Cells, Natural
  • Immunoglobulins
  • Humans
  • Histocompatibility Antigens Class I
  • HLA-E Antigens
  • HLA Antigens
  • Cytotoxicity, Immunologic