Development of antibody-dependent cell cytotoxicity function in HIV-1 antibodies.

Autor:	Doepker LE; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Danon S; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Harkins E; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Ralph DK; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Yaffe Z; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States.; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, United States., Garrett ME; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States.; Molecular and Cellular Biology Graduate Program, University of Washington and Fred Hutchinson Cancer Research Center, Seattle, United States., Dhar A; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.; Department of Statistics, University of Washington, Seattle, United States., Wagner C; Medical Scientist Training Program, University of Washington School of Medicine, Seattle, United States., Stumpf MM; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Arenz D; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Williams JA; Department of Medicinal Chemistry, University of Washington, Seattle, United States., Jaoko W; Department of Medicinal Microbiology, University of Nairobi, Nairobi, Kenya., Mandaliya K; Coast Provincial General Hospital, Women's Health Project, Mombasa, Kenya., Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, United States., Matsen FA 4th; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States., Overbaugh JM; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, United States.; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2021 Jan 11; Vol. 10. Date of Electronic Publication: 2021 Jan 11.
DOI:	10.7554/eLife.63444
Abstrakt:	A prerequisite for the design of an HIV vaccine that elicits protective antibodies is understanding the developmental pathways that result in desirable antibody features. The development of antibodies that mediate antibody-dependent cellular cytotoxicity (ADCC) is particularly relevant because such antibodies have been associated with HIV protection in humans. We reconstructed the developmental pathways of six human HIV-specific ADCC antibodies using longitudinal antibody sequencing data. Most of the inferred naive antibodies did not mediate detectable ADCC. Gain of antigen binding and ADCC function typically required mutations in complementarity determining regions of one or both chains. Enhancement of ADCC potency often required additional mutations in framework regions. Antigen binding affinity and ADCC activity were correlated, but affinity alone was not sufficient to predict ADCC potency. Thus, elicitation of broadly active ADCC antibodies may require mutations that enable high-affinity antigen recognition along with mutations that optimize factors contributing to functional ADCC activity. Competing Interests: LD, SD, EH, DR, ZY, MG, AD, CW, MS, DA, JW, WJ, KM, KL, FM No competing interests declared, JO Reviewing editor, eLife (© 2021, Doepker et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu