7bh8
3H4-Fab HLA-E-VL9 co-complex
Structural highlights
FunctionHLAE_HUMAN Preferably binds to a peptide derived from the signal sequence of most HLA-A, -B, -C and -G molecules. Publication Abstract from PubMedThe 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 naive B cells of cytomegalovirus (CMV)-negative, healthy humans. Thus, HLA-E-VL9-targeting mouse and human antibodies isolated from the naive B cell antibody pool have the capacity to enhance NK cell cytotoxicity. Mouse and human antibodies bind HLA-E-leader peptide complexes and enhance NK cell cytotoxicity.,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 Commun Biol. 2022 Mar 28;5(1):271. doi: 10.1038/s42003-022-03183-5. PMID:35347236[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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