Since the discovery of the T cell receptor in the 1980s, known before as the "Holy Grail of Immunology", many investigations aimed to elucidate its structure and functioning. Our group share the fascination by this unsolved enigma. The T cell receptor is one of the most complex membrane receptors known; it is express on the surface of T cells and it is crucial to initiate the immune responses. Understanding the functioning of the T cell receptor has become most needed in the time of immunotherapy. Chimeric antigen T cells, known as CAR T cells, combine the binding potential of antibodies with the activation potential of the T cell receptor to redirect T cells to target tumours. The high efficiency and potency of CARs to activate T cells is surprising, taking in consideration the complicated, and still unsolved, biology of the TCR. However, this initial enthusiasm has been tempered by the life-threating side effects observed in many clinical CAR trials and the little success in the treatment of solid tumours. In our group, we focus in unravel the mechanisms controlling T cell receptor functioning across scales to innovate in the design of T cell-based immunotherapies against cancer.

Keywords:

Signaling, Immunity, Lymphocyte, T cell, Immunotherapy, Cancer

10 selected publications:

• Phytochrome-Based Extracellular Matrix with Reversibly Tunable Mechanical Properties.
  Hörner M, Raute K, Hummel B, Madl J, Creusen G, Thomas OS, Christen EH, Hotz N, Gübeli RJ, Engesser R, Rebmann B, Lauer J, Rolauffs B, Timmer J, Schamel WWA, Pruszak J, Römer W, Zurbriggen MD, Friedrich C, Walther A, Minguet S, Sawarkar R, Weber W (2019).
  Adv Mater. 31(12):e1806727.
• Caveolin-1: The Unnoticed Player in TCR and BCR Signaling.
  Fiala GJ, Minguet S (2018).
  Adv Immunol. 137:83-133. Caveolin-1-dependent nanoscale organization of the BCR regulates B cell tolerance.
  Minguet S§, Kläsener K, Schaffer AM, Fiala GJ, Osteso-Ibánez T, Raute K, Navarro-Lérida I, Hartl FA, Seidl M, Reth M, Del Pozo MA.
  Nat Immunol. 10:1150-1159. §Corresponding author.
• The Allostery Model of TCR Regulation.
  Schamel WW, Alarcon B, Höfer T, Minguet S (2017).
  J Immunol. 198(1):47-52.
• A cholesterol-based allostery model of T cell receptor phosphorylation.
  Swamy M, Beck-Garcia K, Beck-Garcia E, Hartl FA, Morath A, Yousefi OS, Dopfer EP, Molnár E, Schulze AK, Blanco R, Borroto A, Martín-Blanco N, Alarcon B, Höfer T, Minguet S§, Schamel WW (2016).§
  Immunity. 44(5):1091-101.
  §Corresponding authors.
• Caveolin-1 regulates TCR signal strength and regulatory T cell differentiation into alloreactive T cells
  Schönle A, Hartl FA, Mentzel J, Rauch KS, Wohlfeil SA, Nöltner T, Hechinger AK, Melchinger W, Fehrenbach K, Guadamillas MC, Prestipino A, Follo M, Prinz G, Ruess AK, Pfeifer D, Pozo MA, Schmitt-Graeff A, Duyster J, Blazar BR, Schachtrup K, Minguet S§, Zeiser R§ (2016).
  Blood. 127(15):1930-9.
  §Corresponding authors.
• Kidins220/ARMS binds to the B cell antigen receptor and regulates B cell development and activation
  Fiala GJ, Janowska I, Prutek, F, Hobeika E, Satapathy A, Sprenger A, Plum T, Seidl M, Dengjel J, Reth M, Cesca F, Brummer T, Minguet S§ and Schamel WWA§ (2015).
  J Exp Med 212(10):1693-708.
  §Corresponding authors.
• Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastais.
  Goetz JG*, Minguet S*, Navarro I, Samaniego R, Tello M, Calvo E, Lazcano JJ, Osteso T, Pellinen T, Echarri A, Cerezo A, Garcia R, Keely PJ, Sánchez-Mateos P, Cukierman E, Del Pozo MA (2011).
  Cell. (146):148-63.
  *Shared first authorship.
• Enhanced B cell activation mediated by TLR4 and BCR crosstalk.
  Minguet S§, Huber M, Freudenberg MA, Pollmer C, Reth M, Schamel WW (2008).
  Eur J Immunol. 38(9):2475-87
  §Corresponding author.
• Full activation of the T cell receptor requires both clustering and conformational changes at CD3.
  Minguet S, Swamy M, Alarcon B, Luescher IF, Schamel WW (2007).
  Immunity. (1): 43-54.