University of Minnesota
MICaB Graduate Program
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Current Students

Kotov
Dmitri Kotov

E-mail:kotov003@umn.edu

Thesis Advisor: Marc Jenkins

Year entered: 2012

Degrees received:
B.S., The Ohio State University, Columbus, OH 2012

Honors and Awards:

  • T 32 Immunology Training Grant, 2015 -
  • AAI Trainee Abstract Award, 2014


Research:

The focus of my thesis research is the early drivers of T follicular helper (Tfh) cell differentiation. Tfh cells mediate protective antibody responses by promoting the generation of long-lived plasma cells and memory B cells, thereby dictating vaccine efficacy. Dendritic cells initiate Tfh differentiation while B cells are required for their maintenance. We have identified a significant role for T cell receptor signal (TCR) strength in the generation of Tfh cells at the peak of Listeria infection. We hypothesize that differences in TCR signal strength affect the initial dendritic cell-mediated Tfh differentiation. We are testing this hypothesis with B3K506 and B3K508 TCR transgenic CD4+ T cells, which express TCRs with different affinities for 3K peptide:major histocompatibility complex II. These T cells allow us to examine whether different TCR affinities for the same p:MHCII alter the initial bifurcation into T helper 1 or Tfh cells following Listeria expressing 3K peptide infection. The effect of TCR signal strength on the bifurcation can be driven by variety of pathways downstream of TCR signaling, like cytokine receptor expression. Currently, we are examining the TCR regulated expression of the cytokine receptor IL-2Ra and how this differential expression is affecting the bifurcation. We are also studying the affect of TCR affinity on T cell interactions with dendritic cells in the initial hours of an immune response and how these interactions influence the bifurcation. Collectively, my thesis research will provide insights into early Tfh differentiation thereby providing basic rules for the type of immune response that needs to be generated by a vaccine for optimal T cell help to B cells.

Publications:

  • Spanier JA, Frederick DR,Taylor JJ, Heffernan JR, Matinov T, Kotov D, Ruggerio JL, Rust BJ, Landry SJ, Jenkins MK, McLachlan JB, Fife BT. 2016. Novel approach for the development and antigen-based-enrichment of monoclonal antibodies to peptide in the context of MHC II. Nature Communications. Jun 13;7:11804.
  • Tubo NJ, Fife BT, Pagan AJ, Kotov DI, Goldberg MF, Jenkins MK .2016. Most microbe-specific naïve CD4⁺ T cells produce memory cells during infection. Science. 29;351(6272):511-4
  • Wiesner DL, Smith KD, Kotov DI, Nielsen JN, Bohjanen PR, Nielsen K. 2016. Regulatory T Cell Induction and Retention in the Lungs Drives Suppression of Detrimental Type 2 Th Cells During Pulmonary Cryptococcal Infection. J Immunol. Jan 1;196(1):365-74.
  • Oghumu S, Varikuti S, Terrazas C, Kotov D, Nasser MW, Powell CA, Ganju RK, Satoskar AR. 2014. CXCR3 deficiency enhances tumor progression by promoting macrophage M2 polarization in a murine breast cancer model. Immunology. 143(1):109-19.
  • Nelson, R.W., Beisang, D., Tubo, N.J., Dileepan, T., Wiesner, D.L., Nielson, K.N., Wüthrich, M., Klein, B.S., Kotov, D.I., Spanier, J.A., Fife, B.T., Moon, J.J., Jenkins, M.K. 2014. TCR cross-reactivity between similar foreign and self peptides influences naïve cell population size and autoimmunity. Immunity. 42(1):95-107.