Baoyu Liu Lab
Welcome to the Liu Lab!
Our lab investigates antigen recognition by T cell receptors (TCRs) and B cell receptors (BCRs), the molecular basis of adaptive immunity. Once a T or B cell successfully rearranges and expresses a functional TCR or BCR, its subsequent development, ultimate fate, and antigen-specific responses are largely determined by how that receptor interacts with its cognate antigen. Antibodies—the secreted form of BCRs—similarly depend on antigen binding to mediate effector functions such as antibody-dependent cellular cytotoxicity (ADCC). Our research seeks to define these receptor–antigen interactions by characterizing their binding kinetics and correlating these biophysical properties with downstream immune responses. We further investigate the structural and molecular mechanisms underlying these interactions and leverage these insights to engineer novel receptors and antibodies for therapeutic applications.
A defining feature of TCR and BCR interactions is that they occur at the interface of two opposing cell membranes, where receptor–ligand binding is confined to a two-dimensional (2D) plane. This is fundamentally different from the traditional three-dimensional (3D) measurements of TCR/BCR/antibody binding kinetics that are typically obtained using recombinant proteins in solution. Indeed, 2D and 3D kinetics are physically distinct because they differ in the degrees of freedom governing molecular movement and are often poorly correlated. More importantly, 2D interactions are regulated by the cellular membrane environment and by mechanical forces, factors that are absent in conventional 3D measurements.The significance of these distinctions has been clearly demonstrated in TCR antigen recognition. For example, we and others have shown that 2D kinetic parameters, such as on-rate and affinity, predict T cell responses more accurately than their 3D counterparts. In addition, TCR catch bonds—interactions that strengthen under mechanical force—play critical roles in thymic selection as well as antiviral and antitumor immunity. Building on these findings, we are interested in exploring analogous mechanisms in BCR antigen recognition.
Our research employs a broad range of experimental and computational approaches, including mouse, humanized mouse, and human systems to study T and B cell function; ultrasensitive biophysical techniques such as the biomembrane force probe to quantify 2D binding kinetics; phage display to generate novel antibodies; and molecular dynamics simulations and mutagenesis studies to guide molecular engineering strategies.
Our current work focuses on self-antigen recognition by autoimmune T cells in type 1 diabetes and rheumatoid arthritis, where we have identified kinetic features unique to self-reactivity that are not observed in conventional foreign antigen recognition. We are also extending the 2D framework to additional areas of B cell biology, including the development of antibodies targeting distinctive features of self-antigen recognition and the engineering of antibodies to improve the efficacy and persistence of chimeric antigen receptor (CAR) T cell therapies.
Baoyu Liu
Assistant Professor
Department of Pathology
University of Utah School of Medicine
Contact Us
Emma Eccles Jones Medical Research Building
15 North Medical Drive East
Room 1820
Salt Lake City, UT 84112
Lab Phone: 801-585-2156
Office Phone: 801-585-2131
Email: baoyu.liu@path.utah.edu
Lab Members
Select Publications
Selected Publications
Baoyu Liu*, Elizabeth M Kolawole*, Brian D Evavold. Mechanobiology of T Cell Activation: To Catch a Bond. Annu. Rev. Cell Dev. Biol. 2021. 37:65-87. PMID: 34213954. *Equal authorship.
Baoyu Liu*, Jennifer D Hood*, Elizabeth M Kolawole, Derek M Woodruff, Dario A Vignali, Maria Bettini, Brian D Evavold. A Hybrid Insulin Epitope Maintains High 2D Affinity for Diabetogenic T Cells in the Periphery. Diabetes. 2020. 69(3):381-391. PMCID: PMC7034185. *Equal authorship.
Maria Bettini, Marissa A Scavuzzo, Baoyu Liu, Elizabeth Kolawole, Lin Guo, Brian D Evavold, Malgorzata Borowiak, Matthew L Bettini. A Critical Insulin TCR Contact Residue Selects High Affinity and Pathogenic Insulin Specific T Cells. Diabetes. 2020. 69(3):392-400.
Peng Wu*, Tongtong Zhang*, Baoyu Liu*, Panyu Fei*, Lei Cui*, Rui Qin, Huaying Zhu, Danmei Yao, Ryan J Martinez, Wei Hu, Chenyi An, Yong Zhang, Junwei Liu, Jiawei Shi, Juan Fan, Weiwei Yin, Jie Sun, Chun Zhou, Xun Zeng, Chenqi Xu, Jianan Wang, Brian D Evavold, Cheng Zhu, Wei Chen, Jizhong Lou. Mechano-regulation of Peptide-MHC Class I Conformations Determines TCR Antigen Recognition. Mol. Cell. 2019. doi:10.1016/j.molcel.2018.12.018 * Equal authorship.
Jinsung Hong, Chenghao Ge, Prithiviraj Jothikumar, Zhou Yuan, Baoyu Liu, Ke Bai, Kaitao Li, William Rittase, Miho Shinzawa, Yun Zhang, Amy Palin, Paul Love, Xinhua Yu, Khalid Salaita, Brian D Evavold, Alfred Singer, Cheng Zhu. A TCR mechanotransduction signaling loop induces negative selection in the thymus. Nat. Immunol. 2018. 19(12): 1379–1390.
Lining Ju, Yunfeng Chen, Kaitao Li, Yuan Zhou, Baoyu Liu, Shaun P Jackson, Cheng Zhu. Dual Biomembrane Force Probe enables single-cell mechanical analysis of signal crosstalk between multiple molecular species. Sci. Rep. 2017. 7, 1(14185).
Yunfeng Chen*, Baoyu Liu*, Lining Ju*, Jinsung Hong, Qinghua Ji, Wei Chen, Cheng Zhu. Fluorescence Biomembrane Force Probe: Concurrent Quantitation of Receptor-Ligand Kinetics and Binding-induced Intracellular Signaling on a Single Cell. JoVE. 2015. (102), e52975. *Equal authorship.
Baoyu Liu, Wei Chen, and Cheng Zhu. Molecular Force Spectroscopy on Cells. Annu. Rev. Phys. Chem. 2015. 66: 427-451.
Baoyu Liu*, Wei Chen*, Brian D. Evavold, and Cheng Zhu. Accumulation of Dynamic Catch Bonds between TCR and Agonist Peptide-MHC Triggers T Cell Signaling. Cell. 2014. 157(2): 357-368. *Equal authorship.
Jarrett J. Adams, Sami Narayanan, Baoyu Liu, Michael E. Birnbaum, Andrew Kruse, Natalie A. Bowerman, Wei Chen, Aron M. Levin, Janet M. Connolly, Cheng Zhu, David M. Kranz, and K. Christopher Garcia. T Cell Receptor Signaling is Limited by Docking Geometry to Peptide-MHC. Immunity. 2011. 35(5): 681-693.
Ning Jiang, Jun Huang, Lindsay J. Edwards, Baoyu Liu, Yan Zhang, Carrie D. Beal, Brian D. Evavold, and Cheng Zhu. Two-Stage Cooperative T Cell Receptor-Peptide Major Histocompatibility Complex-CD8 Trimolecular Interactions Amplify Antigen Discrimination. Immunity. 2011. 34(1):13-23.
Jun Huang, Veronika I. Zarnitsyna, Baoyu Liu, Lindsay J. Edwards, Ning Jiang, Brian D. Evavold, and Cheng Zhu. The Kinetics of Two Dimensional TCR and pMHC Interactions Determine T Cell Responsiveness. Nature. 2010. 464(7290): 932–936.