Costimulator

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A costimulator (synonymous with a costimulatory molecule ) is a protein that has to be activated as a second receptor in order to trigger an adaptive immune response .

properties

The adaptive immune response arises through antigen presentation to the B-cell receptor (BCR) on B-cells and to MHC to the T-cell receptor (TCR) of T-cells . Activation only takes place if a second receptor from the group of costimulators is activated at the same time. If the BCR or TCR is activated without activating a costimulator, anergy occurs .

B cells

Examples of co-stimulators in B cells are CD40 and its ligand CD40L , or CR2 and one of its ligands iC3b , C3dg or C3d .

T cells

Co-stimulators in T cells are CD28 and its ligands B7-1 and B7-2 , as well as ICOS and its ligand ICOSL (synonym B7-H2 ). The binding of CD28 is competitively inhibited by the immunosuppressive receptor CTLA-4 .

Some superantigens bind to the TCR and to the co-stimulator CD28 at the same time, whereby both signals necessary for activation of the T cell are transmitted.

Applications

Abatacept and Belatacept are each fusion proteins of the Fc region of IgG 1 with the extracellular portion of CTLA4 that bind to B7 proteins and the costimulation of T cells suppress. Abatacept is used to treat the autoimmune disease rheumatoid arthritis . Belatacept is used to prevent rejection after a kidney transplant . Inhibiting costimulators is being investigated for the treatment of the autoimmune disease lupus erythematosus . Furthermore, an inhibition of costimulators for the treatment of organ-specific autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus is being investigated.

Individual evidence

  1. ^ V. Seda, M. Mraz: B-cell receptor signaling and its crosstalk with other pathways in normal and malignant cells. In: European journal of haematology. Volume 94, number 3, March 2015, pp. 193-205, doi: 10.1111 / ejh.12427 , PMID 25080849 .
  2. ↑ K. Frank, JP Atkinson: Complement system. In: Austen KF, Frank K, Atkinson JP, Cantor H. eds. Samter's Immunologic Diseases, 6th ed. Vol. 1, Philadelphia: Lippincott Williams & Wilkins, 2001. ISBN 0-7817-2120-2 . Pp. 281-298.
  3. ^ Peter Parham: The Immune System, Fourth Edition. Garland Science, 2014, ISBN 978-1-317-51157-1 , p. 211.
  4. ↑ Richard Coico: Immunology. John Wiley & Sons, 2015, ISBN 978-1-118-39690-2 .
  5. ↑ ML Ford, AB Adams, TC Pearson: Targeting co-stimulatory pathways: transplantation and autoimmunity. In: Nature reviews. Nephrology. Volume 10, number 1, January 2014, pp. 14-24, doi: 10.1038 / nrneph.2013.183 , PMID 24100403 , PMC 4365450 (free full text).
  6. ↑ L. Chen, DB Flies: Molecular mechanisms of T cell co-stimulation and co-inhibition. In: Nature Reviews Immunology . Volume 13, number 4, April 2013, pp. 227-242, doi : 10.1038 / nri3405 , PMID 23470321 , PMC 3786574 (free full text).
  7. ↑ N. Beyersdorf, T. Kerkau, T. Hünig: CD28 co-stimulation in T-cell homeostasis: a recent perspective. In: ImmunoTargets and therapy. Volume 4, 2015, pp. 111-122, doi : 10.2147 / ITT.S61647 , PMID 27471717 , PMC 4918251 (free full text).
  8. ↑ Inca Sastalla: Bacterial exotoxin: How Bacteria Fight the Immune System. Frontiers Media SA, 2016, ISBN 978-2-88919-991-4 , p. 155.
  9. ↑ L. Moreland, G. Bate, P. Kirkpatrick: Abatacept. In: Nature reviews. Drug discovery. Volume 5, number 3, 03 2006, pp. 185-186, doi: 10.1038 / nrd1989 , PMID 16557658 .
  10. ^ P. Masson, L. Henderson, JR Chapman, JC Craig, AC Webster: Belatacept for kidney transplant recipients. In: The Cochrane database of systematic reviews. Number 11, November 2014, p. CD010699, doi: 10.1002 / 14651858.CD010699.pub2 , PMID 25416857 .
  11. ↑ ML Ford, AB Adams, TC Pearson: Targeting co-stimulatory pathways: transplantation and autoimmunity. In: Nature reviews. Nephrology. Volume 10, number 1, January 2014, pp. 14-24, doi: 10.1038 / nrneph.2013.183 , PMID 24100403 , PMC 4365450 (free full text).
  12. ^ Q. Zhang, DA Vignali: Co-stimulatory and Co-inhibitory Pathways in Autoimmunity. In: Immunity. Volume 44, number 5, May 2016, pp. 1034-1051, doi: 10.1016 / j.immuni.2016.04.017 , PMID 27192568 , PMC 4873959 (free full text).