New Methods for Studying and Designing pMHC-TCR Interactions

New Methods for Studying and Designing pMHC-TCR Interactions

T cell mediated immunity involves immense molecular diversity on the pMHC and TCR sides. Mapping TCRs to the pMHCs they recognize will aid in understanding disease biology, creating immunotherapies, and improving computational prediction tools. Existing antigen discovery tools are limited in scale; they allow screens of a large number of pMHC molecules against a small number of TCRs, or a small number of pMHC molecules against a large number of TCRs, but a gap remains in technologies for screening many pMHCs against many TCRs. We develop new approaches across a wide array of modalities to enable high-throughput antigen discovery screens.

Our lab balances method development, fundamental immunology, and engineering. We use antigen discovery tools to better understand immune responses in the context of cancer, infection, autoimmunity, and transplantation. We also aim to design novel immunotherapies and vaccines, and to train algorithms that can accurately predict and design antigen recognition.


Selected publications:

Antigen identification and high-throughput interaction mapping by reprogramming viral entry. Dobson, C. S., Reich, A. N., Gaglione, S., Smith, B. E., Kim, E. J., Dong, J., Ronsard, L., Okonkwo, V., Lingwood, D., Dougan, M., Dougan, S. K., & Birnbaum, M. E. Nature Methods, 19(4), 449–460 (2022). https://doi.org/10.1038/s41592-022-01436-z

Repertoire-scale determination of class II MHC peptide binding via yeast display improves antigen prediction. Rappazzo, C. G., Huisman, B. D., & Birnbaum, M. E. Nature Communications, 11(1) (2020). https://doi.org/10.1038/s41467-020-18204-2

A high-throughput yeast display approach to profile pathogen proteomes for MHC-II binding. Huisman, B. D., Dai, Z., Gifford, D. K., & Birnbaum, M. E. ELife, 11 (2022). https://doi.org/10.7554/elife.78589

High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation. Huisman, B. D., Guan, N., Rückert, T., Garner, L., Singh, N. K., McMichael, A. J., Gillespie, G. M., Romagnani, C., & Birnbaum, M. E. Nature Communications, 14(1) (2023). https://doi.org/10.1038/s41467-023-40220-1