Immunology Faculty Member - Daniel Lingwood, PhD

Daniel Lingwood, PhD

Ragon Institute of MGH, MIT and Harvard
400 Technology Square, Room 768

Cambridge, MA 02139
Tel: 857-268-7180
Email: dlingwood@mgh.harvard.edu



Our research centers on defining biochemical and biophysical principles of antigen recognition to inform on the design of viral vaccines.

The mechanism by which the germline B cell receptor (BCR) engages antigen prior to development of immunological memory is not well understood. New antigen-specific BCR sequences can arise through VDJ recombination and stochastic diversification of the germline antibody repertoire, however, conserved features in humoral responses to some viruses has prompted us to hypothesize that the adaptive immune system is also endowed with innate-like pattern recognition motifs that de-randomize the epitope upon which antibody responses center. This has lead to our discovery that humans possess genetically-encoded B cell receptor (BCR) sequences that naturally engage conserved sites of viral vulnerability, serving as substrates for the development of pan-neutralizing humoral responses. Interestingly, this pattern recognition depends critically on membrane surface orientation of antibody paratopes, highlighting an unexpected physical contribution to innate-like antigen recognition. We now use a combination of reconstituted BCR signaling and immunization studies to examine how this kind of pattern-recognition and B cell surface organization can be exploited to engender effective humoral responses, primarily to influenza virus and HIV.

Questions we currently exploring:
1) Can reconstituted BCR-antigen interactions predict and rank-order vaccine activity prior to use?

2) Do other conserved BCR motifs in addition to the specific germline V sequences serve as pattern-recognition motifs?

3) How does pattern-recognition shape humoral responses to vaccine targets?

4) How are vaccine antigens physically presented to the naïve BCR in vivo?



Last Update: 3/26/2019



Publications

Weaver GC, Villar RF, Kanekiyo M, Nabel GJ, Mascola JR, Lingwood D. 2016. In Vitro Reconstitution of B Cell Receptor Antigen Interactions to Evaluate Potential Vaccine Candidates. Nature Protocols 11:193-213. PMID: 26741406

Villar, RF, Patel, Weaver GC, Kanekiyo M, Wheatley AK, Yassine HM, Costello CE, Chandler KB, McTamney PM, Nabel GJ, McDermott AB, Mascola JR, Carr SA and Lingwood D. 2016. Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation. Scientific Reports 6:36298. PMID: 27796362

Lingwood, D. 2014. Lipocalin 2 as a Membrane Reorganizing Agent. Science Signaling 7:pe19. PMID: 25118326

Lingwood, D, McTamney PM, Yassine HM, Whittle JR, Guo X, Boyington JC, Wei C-J, Nabel G. 2012. Structural and Genetic Basis for Development of Broadly Neutralizing Influenza Antibodies. Nature 489:566-570. PMID: 22932267

Lingwood, D, Binnington B, Róg T, Vattulainen I, Grzybek M, Coskun U, Lingwood CA, Simons K 2011. Cholesterol modulates glycolipid conformation and receptor activity. Nature Chemical Biology 7:260-262. PMID: 21460830



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of Harvard College