Stanford Advisors

All Publications

  • Disease diagnostics using machine learning of B cell and T cell receptor sequences. Science (New York, N.Y.) Zaslavsky, M. E., Craig, E., Michuda, J. K., Sehgal, N., Ram-Mohan, N., Lee, J. Y., Nguyen, K. D., Hoh, R. A., Pham, T. D., Röltgen, K., Lam, B., Parsons, E. S., Macwana, S. R., DeJager, W., Drapeau, E. M., Roskin, K. M., Cunningham-Rundles, C., Moody, M. A., Haynes, B. F., Goldman, J. D., Heath, J. R., Chinthrajah, R. S., Nadeau, K. C., Pinsky, B. A., Blish, C. A., Hensley, S. E., Jensen, K., Meyer, E., Balboni, I., Utz, P. J., Merrill, J. T., Guthridge, J. M., James, J. A., Yang, S., Tibshirani, R., Kundaje, A., Boyd, S. D. 2025; 387 (6736): eadp2407

    Abstract

    Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune system's own record of antigen exposures encoded by receptors on B cells and T cells. We analyzed immune receptor datasets from 593 individuals to develop MAchine Learning for Immunological Diagnosis, an interpretive framework to screen for multiple illnesses simultaneously or precisely test for one condition. This approach detects specific infections, autoimmune disorders, vaccine responses, and disease severity differences. Human-interpretable features of the model recapitulate known immune responses to severe acute respiratory syndrome coronavirus 2, influenza, and human immunodeficiency virus, highlight antigen-specific receptors, and reveal distinct characteristics of systemic lupus erythematosus and type-1 diabetes autoreactivity. This analysis framework has broad potential for scientific and clinical interpretation of immune responses.

    View details for DOI 10.1126/science.adp2407

    View details for PubMedID 39977494

  • KIR+CD8+ T cells suppress pathogenic T cells and are active in autoimmune diseases and COVID-19. Science (New York, N.Y.) Li, J., Zaslavsky, M., Su, Y., Guo, J., Sikora, M. J., van Unen, V., Christophersen, A., Chiou, S., Chen, L., Li, J., Ji, X., Wilhelmy, J., McSween, A. M., Palanski, B. A., Mallajosyula, V. V., Bracey, N. A., Dhondalay, G. K., Bhamidipati, K., Pai, J., Kipp, L. B., Dunn, J. E., Hauser, S. L., Oksenberg, J. R., Satpathy, A. T., Robinson, W. H., Dekker, C. L., Steinmetz, L. M., Khosla, C., Utz, P. J., Sollid, L. M., Chien, Y., Heath, J. R., Fernandez-Becker, N. Q., Nadeau, K. C., Saligrama, N., Davis, M. M. 2022: eabi9591

    Abstract

    Here we find that CD8+ T cells expressing inhibitory killer cell immunoglobulin-like receptors (KIRs) are the human equivalent of Ly49+CD8+ regulatory T cells in mice and are increased in the blood and inflamed tissues of patients with a variety of autoimmune diseases. Moreover, these CD8+ T cells efficiently eliminated pathogenic gliadin-specific CD4+ T cells from celiac disease patients' leukocytes in vitro. We also find elevated levels of KIR+CD8+ T cells, but not CD4+ regulatory T cells, in COVID-19 patients, which correlated with disease severity and vasculitis. Selective ablation of Ly49+CD8+ T cells in virus-infected mice led to autoimmunity post infection. Our results indicate that in both species, these regulatory CD8+ T cells act uniquely to suppress pathogenic T cells in autoimmune and infectious diseases.

    View details for DOI 10.1126/science.abi9591

    View details for PubMedID 35258337

  • Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination. Cell Röltgen, K., Nielsen, S. C., Silva, O., Younes, S. F., Zaslavsky, M., Costales, C., Yang, F., Wirz, O. F., Solis, D., Hoh, R. A., Wang, A., Arunachalam, P. S., Colburg, D., Zhao, S., Haraguchi, E., Lee, A. S., Shah, M. M., Manohar, M., Chang, I., Gao, F., Mallajosyula, V., Li, C., Liu, J., Shoura, M. J., Sindher, S. B., Parsons, E., Dashdorj, N. J., Dashdorj, N. D., Monroe, R., Serrano, G. E., Beach, T. G., Chinthrajah, R. S., Charville, G. W., Wilbur, J. L., Wohlstadter, J. N., Davis, M. M., Pulendran, B., Troxell, M. L., Sigal, G. B., Natkunam, Y., Pinsky, B. A., Nadeau, K. C., Boyd, S. D. 2022

    Abstract

    During the SARS-CoV-2 pandemic, novel and traditional vaccine strategies have been deployed globally. We investigated whether antibodies stimulated by mRNA vaccination (BNT162b2), including third-dose boosting, differ from those generated by infection or adenoviral (ChAdOx1-S and Gam-COVID-Vac) or inactivated viral (BBIBP-CorV) vaccines. We analyzed human lymph nodes after infection or mRNA vaccination for correlates of serological differences. Antibody breadth against viral variants is lower after infection compared with all vaccines evaluated but improves over several months. Viral variant infection elicits variant-specific antibodies, but prior mRNA vaccination imprints serological responses toward Wuhan-Hu-1 rather than variant antigens. In contrast to disrupted germinal centers (GCs) in lymph nodes during infection, mRNA vaccination stimulates robust GCs containing vaccine mRNA and spike antigen up to 8 weeks postvaccination in some cases. SARS-CoV-2 antibody specificity, breadth, and maturation are affected by imprinting from exposure history and distinct histological and antigenic contexts in infection compared with vaccination.

    View details for DOI 10.1016/j.cell.2022.01.018

    View details for PubMedID 35148837