Draft:Willi Born

Born in Frankfurt, Germany, on April 24th 1952, Willi K. Born grew up in Freiburg, Germany. During his graduate work in immunology, he investigated autoimmunity in alpha beta T cells. His dissertation focused on immunological autoreactivity.^{[1] [2]} After earning his doctorate in immunology in 1982, he moved to the United States for immunological research. During his professional career, he studied gamma delta T cells, mainly in collaboration with fellow immunologist Rebecca L. O'Brien. In 1988, he and Rebecca were married. Together, they have two daughters.

Born completed both undergraduate and graduate studies at the Albert Ludwig University in Freiburg, Germany. He did research for his degrees at what was then the Max Planck Institute for Immunobiology, now the Max Planck Institute of Immunobiology and Epigenetics, under the guidance of Marie Luise Lohmann-Matthes, and Hartmut Wekerle, the latter whom he credits for eliciting his interest in T cells.

In 1982, he moved to the United States after graduation, first to Dallas, TX, for training in molecular genetics with Haley Tucker, and later to Denver, CO, for further studies on T cells and the then recently discovered alpha beta T cell receptor for antigen (TCR) with Philippa Marrack, and John Kappler.

In 1987, Born obtained his first faculty position at the University of Colorado. In 1989, Born and O'Brien formed a joint research group at National Jewish Health for studies on the newly discovered gamma delta T cells. There was substantial skepticism regarding these cells at the time. Born worked on increasing understanding about gamma delta T cells, and authored or co-authored approximately 200 scientific publications^[3] and educational reviews. Having retired in 2018, Born is an emeritus professor at National Jewish Health.^[4]

Mentored by Philippa Marrack and trained by molecular biologist Ed Palmer, Born used hybridoma technology with the T cell fusion line BW5147^[5] to analyze T cells developing in the fetal thymus and demonstrate the ordered progression of TCR gene rearrangements during T cell maturation^[6][7].

Together with research technologist Janice White, he then modified the fusion line by disabling its endogenous alpha and beta TCR genes through radiation mutagenesis^[8], facilitating further studies on T cell specificity.

Silencing endogenous TCR alpha in the fusion line also increased permissiveness for expression of another cell surface-expressed protein dimer, gamma delta, which had been proposed to be a second TCR^[9][10]. This was an unforeseen outcome. Taking advantage, Born produced gamma delta+ hybridomas with fetal thymocytes. Encouraged by John Kappler, he worked together with investigators in the department to purify the gamma delta heterodimer from one of these hybridomas and sequence fragments of both proteins^[11]. The protein sequences showed that a newly discovered TCR gene^[12] indeed encoded the delta chain, and they confirmed the TCR nature of the gamma delta heterodimer^[11]. These findings established gamma delta-expressing cells as a second type of T cell with variable, adaptive TCRs^[13]

Born and collaborator O'Brien then started a joint research group (BOB lab) to study the new T cells. Because of greater accessibility, the work was done in mice. Apart from the lymphoid tissues, BOB lab researchers investigated and compared gamma delta T cell populations in the skin^[14], mammary gland^[15], placenta^[16], liver^[17], lung^[18] and pancreas^[19]. They noted numerous connections between gamma delta T cells and other cells of the immune system such as B cells^[20], alpha beta T cells including NKT cells^[21][22], and dendritic cells^[23], but also with trophoblasts^[24].

Using gamma delta TCR+ hybridomas, they screened for specificity. In addition to finding anti-bacterial^[25] responses dependent on the gamma delta TCR, they reported specific recognition of diverse structurally defined molecules, both peptidic and non-peptidic^[26][27]. Hallmarks of stimulatory peptides identified in these early studies re-emerged in present day efforts to vaccinate against SARS-CoV-2^[28].

Gamma delta-TCR-dependent recognition of peptides did not require antigen presentation^[29], unlike the antigen recognition by alpha beta T cells.

BOB lab investigators saw that gamma delta T cells in vivo were mainly engaged in regulation, in keeping with their small numbers in rodents. They found them to modulate inflammation^[30], but also normal lymphocyte development^[31]. Collaborating with Sally Huber at the University of Vermont, they observed that the regulatory effect could be based on a balance between counter-reactive subsets of gamma delta T cells^[32][33]. Tipping this balance, they noted vast physiological changes, for example in airway function during allergic responses^[34], with steady state circulating antibody levels^[35], or with the pre-immune composition of B cell and alpha beta T cell populations^[31][21]. The BOB lab data identified gamma delta T cells as a potential target of immune intervention.^[36][37][38]

Born served on the editorial boards of immunological journals, as guest editor for the Proceedings of the National Academy of Sciences, USA, and as reviewer for scientific journals such as Cell, Science, Nature, Journal of Experimental Medicine, and Journal of Immunology. He served as member on the Arthritis Foundation study section and as ad hoc reviewer for NIH study sections and for the Welcome Trust. He was a member of the American Association of Immunologists (AAI) and the German Immunological Society, and he served on the scientific advisory board of the Institute for Human Virology in Baltimore.

In 2004, to promote scientific exchange and improve access for young investigators to the emerging field, Born and O'Brien started in Denver, CO what became a series of international conferences exclusively dedicated to gamma delta T cells, held biannually in different locations under the auspices of local immunologists.^[39] Born and O’Brien continued to promote the conferences as scientific advisors, session chairs and presenters and over time, participation quadrupled. To date, 11 conferences in the USA, Europe, and China have taken place:

• 2004 – Denver, CO
• 2006 – La Jolla, CA
• 2008 – Marseille, France
• 2010 – Kiel, Germany
• 2012 – Freiburg, Germany
• 2014 – Chicago, IL
• 2016 – London, United Kingdom
• 2018 – Bordeaux, France
• 2020 – Cancelled: SARS-CoV-2 pandemic
• 2021 – Zhuhai, China
• 2023 – Lisbon, Portugal
• 2025 – Toronto, Canada

At National Jewish Health, Born served as interim director of the Biological Resources Center for which he received the 2006 Faculty Citizen of the Year Award, and also served as director of flow cytometry.

• Fellow, Studienstiftung (German Academic Scholarship Foundation)
• Fellow, Deutsche Forschungsgemeinschaft (German Research Foundation)
• Associate Editor, Journal of Immunology
• Investigator Award, Cancer Research Institute
• Member, Arthritis Foundation Study Section
• Visiting Professor, Peking Union Medical College, Beijing, China
• Faculty Citizen of the Year, National Jewish Health