regulatory T cell; TCR affinity; CD4+ T cell; infection; asymmetric division
Schreiner David, King Carolyn G. (2018), CD4+ Memory T Cells at Home in the Tissue: Mechanisms for Health and Disease, in Frontiers in Immunology
, 9, 1.
Wyss Lena, Stadinski Brian D, King Carolyn G, Schallenberg Sonja, McCarthy Nicholas I, Lee Jun Young, Kretschmer Karsten, Terracciano Luigi M, Anderson Graham, Surh Charles D, Huseby Eric S, Palmer Ed (2016), Affinity for self antigen selects Treg cells with distinct functional properties., in Nature immunology
, 17(9), 1093-101.
Balmer Maria L, Ma Eric H, Bantug Glenn R, Grählert Jasmin, Pfister Simona, Glatter Timo, Jauch Annaïse, Dimeloe Sarah, Slack Emma, Dehio Philippe, Krzyzaniak Magdalena A, King Carolyn G, Burgener Anne-Valérie, Fischer Marco, Develioglu Leyla, Belle Réka, Recher Mike, Bonilla Weldy V, Macpherson Andrew J, Hapfelmeier Siegfried, Jones Russell G, Hess Christoph (2016), Memory CD8(+) T Cells Require Increased Concentrations of Acetate Induced by Stress for Optimal Function., in Immunity
, 44(6), 1312-24.
CD4+ T cells are critical regulators of health and disease. Defects in T cell function can result in a variety of immune disorders including susceptibility to infection and the development of autoimmunity. T cell receptor (TCR) recognition of peptide:MHC (pMHC) is an essential first step in the initiation of a T cell response. Although the strength of TCR-pMHC interactions has been shown to directly modulate T cell fitness and clonal dominance within the Th compartment, how this influences effector and memory differentiation during infection is not well understood. Our preliminary data reveal distinct influences of antigen affinity and antigen dose on CD4+ T cells responding during infection. How these differences are initiated at the TCR signaling level and translated into diverse cell fates is currently unknown. Using models of both infection and tolerance my lab will focus on two broad questions: (i) how does TCR signal strength regulate the quality and extent of CD4 differentiation; and (ii) what are the molecular mechanisms that link TCR signal strength with the generation of heterogeneous CD4+T cell fates?