Inhibition of Ly-49/LILRB-MHC-I interactions by anti-MHC-I augments innate and adaptive immunity.

نویسندگان

چکیده

Abstract Mouse NK cells recognize MHC-I antigens via stochastically expressed inhibitory Ly49 receptors. The loss of expression on tumor (“missing self”) abrogates signals, resulting in activation. We have identified an anti-mouse pan mAb (M1/42), which blocks Ly49-MHC-I interactions but not TCR-MHC-I interactions. Administration M1/42 vivo markedly activated IFNg-producing that further drove the proliferation and memory phenotype (MP) T profoundly augmented adaptive immunity against viral infection cancer metastasis. In contrast to mouse Ly-49 antigens, human killer cell receptors bind HLA at a site overlapping TCR binding blocking KIR would inhibit recognition. However, two anti-pan-human abs (DX17 W6/32) induced IFNg production cultures PBMC. DX17 potently blocked interaction leukocyte Ig-like LILRB1, B2, B3 B5 with had no effect crystal structure Fab/MHC-I complex reveals footprint overlaps LILRB1 MHC-I. W6/32 Fab humanized mice (PBMC reconstituted NSG or NOG-IL-15) MP proliferation. Marked reduction size was seen when NOG-hIL-15Tg were CD3 −cells then treated Fab. Fc silenced LALAPG) infiltrating lymphocytes monocytes. These results strongly suggest inhibition LILRB-MHC-I by anti-MHC-I humans may result marked augmentation anti-tumor immunity. This work supported Intramural Research Program NIAID, NIH.

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ژورنال

عنوان ژورنال: Journal of Immunology

سال: 2023

ISSN: ['1550-6606', '0022-1767']

DOI: https://doi.org/10.4049/jimmunol.210.supp.169.14