Sequence and functional characterization of a public HIV-specific antibody clonotype

Amyn A Murji; Nagarajan Raju; Juliana S Qin; Haajira Kaldine; Katarzyna Janowska; Emilee Friedman Fechter; Rutendo Mapengo; Cathrine Scheepers; Ian Setliff; Priyamvada Acharya; Lynn Morris; Ivelin S Georgiev

doi:10.1016/j.isci.2021.103564

Sequence and functional characterization of a public HIV-specific antibody clonotype

iScience. 2021 Dec 3;25(1):103564. doi: 10.1016/j.isci.2021.103564. eCollection 2022 Jan 21.

Authors

Amyn A Murji^{1

2}, Nagarajan Raju^{1

2}, Juliana S Qin², Haajira Kaldine^{3

4}, Katarzyna Janowska^{5

6}, Emilee Friedman Fechter², Rutendo Mapengo^{3

4}, Cathrine Scheepers^{3

4}, Ian Setliff², Priyamvada Acharya^{5

6}, Lynn Morris^{3

4

7}, Ivelin S Georgiev^{1

2

8

9

10

11}

Affiliations

¹ Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
² Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
³ National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa.
⁴ Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa.
⁵ Division of Structural Biology, Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
⁶ Department of Surgery, Duke University School of Medicine, Durham, NC 27710, USA.
⁷ Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban 4041, South Africa.
⁸ Program in Computational Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
⁹ Vanderbilt Institute for Infection, Immunology and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
¹⁰ Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN 37232, USA.
¹¹ Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.

Abstract

Public antibody clonotypes shared among multiple individuals have been identified for several pathogens. However, little is known about the determinants of antibody "publicness". Here, we characterize the sequence and functional properties of antibodies from a public clonotype targeting the CD4 binding site on HIV-1 Env. Our results showed that HIV-1 specificity for the public antibodies studied here, comprising sequences from three individuals, was modulated by the V_H, but not V_L, germline gene. Non-native pairing of public heavy and light chains from different individuals suggested functional complementation of sequences within this public antibody clonotype. The strength of antigen recognition appeared to be dependent on the specific antibody light chain used, but not on other sequence features such as native-antibody or germline sequence identity. Understanding the determinants of antibody clonotype "publicness" can provide insights into the fundamental rules of host-pathogen interactions at the population level, with implications for clonotype-specific vaccine development.

Keywords: Immunology; Virology.

Abstract

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