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All Publications

  • A Circulating Bioreactor Reprograms Cancer Cells Toward a More Mesenchymal Niche ADVANCED BIOSYSTEMS Calamak, S., Ermis, M., Sun, H., Islam, S., Sikora, M., Nguyen, M., Hasirci, V., Steinmetz, L. M., Demirci, U. 2020
  • Select sequencing of clonally expanded CD8(+) T cells reveals limits to clonal expansion PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Huang, H., Sikora, M. J., Islam, S., Chowdhury, R., Chien, Y., Scriba, T. J., Davis, M. M., Steinmetz, L. M. 2019; 116 (18): 8995–9001
  • Select sequencing of clonally expanded CD8+ T cells reveals limits to clonal expansion. Proceedings of the National Academy of Sciences of the United States of America Huang, H., Sikora, M. J., Islam, S., Chowdhury, R. R., Chien, Y., Scriba, T. J., Davis, M. M., Steinmetz, L. M. 2019


    To permit the recognition of antigens, T cells generate a vast diversity of T cell receptor (TCR) sequences. Upon binding of the TCR to an antigen-MHC complex, T cells clonally expand to establish an immune response. To study antigen-specific T cell clonality, we have developed a method that allows selection of rare cells, based on RNA expression, before in-depth scRNA-seq (named SELECT-seq). We applied SELECT-seq to collect both TCR sequences and then transcriptomes from single cells of peripheral blood lymphocytes activated by a Mycobacterium tuberculosis (Mtb) lysate. TCR sequence analysis allowed us to preferentially select expanded conventional CD8+ T cells as well as invariant natural killer T (iNKT) cells and mucosal-associated invariant T (MAIT) cells. The iNKT and MAIT cells have a highly similar transcriptional pattern, indicating that they carry out similar immunological functions and differ considerably from conventional CD8+ T cells. While there is no relationship between expression profiles and clonal expansion in iNKT or MAIT cells, highly expanded conventional CD8+ T cells down-regulate the interleukin 2 (IL-2) receptor alpha (IL2RA, or CD25) protein and show signs of senescence. This suggests inherent limits to clonal expansion that act to diversify the T cell response repertoire.

    View details for PubMedID 30992377

  • Opposing T cell responses in experimental autoimmune encephalomyelitis. Nature Saligrama, N., Zhao, F., Sikora, M. J., Serratelli, W. S., Fernandes, R. A., Louis, D. M., Yao, W., Ji, X., Idoyaga, J., Mahajan, V. B., Steinmetz, L. M., Chien, Y. H., Hauser, S. L., Oksenberg, J. R., Garcia, K. C., Davis, M. M. 2019


    Experimental autoimmune encephalomyelitis is a model for multiple sclerosis. Here we show that induction generates successive waves of clonally expanded CD4+, CD8+ and γδ+ T cells in the blood and central nervous system, similar to gluten-challenge studies of patients with coeliac disease. We also find major expansions of CD8+ T cells in patients with multiple sclerosis. In autoimmune encephalomyelitis, we find that most expanded CD4+ T cells are specific for the inducing myelin peptide MOG35-55. By contrast, surrogate peptides derived from a yeast peptide major histocompatibility complex library of some of the clonally expanded CD8+ T cells inhibit disease by suppressing the proliferation of MOG-specific CD4+ T cells. These results suggest that the induction of autoreactive CD4+ T cells triggers an opposing mobilization of regulatory CD8+ T cells.

    View details for DOI 10.1038/s41586-019-1467-x

    View details for PubMedID 31391585