Antigen shedding

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Schematic representation of the antigen shedding with an ADAM metalloprotease.

In immunology, the term antigen shedding is understood to mean the repulsion of antigens from the cell membrane of body cells . The term is mainly used in oncology . Antigen shedding is a special form of ectodomain shedding (" shedding an outer domain"), in which membrane proteins are generally detached from the cell membrane.

description

When antigen-shedding which is antigen expression upregulated. The tumor cells concentrate the membrane antigens in an area of the cell membrane ( Engl. Capping = "cover education") and then throw them into the interstitial space as free soluble antigens from (Engl. Shedding = "drop"). The detachment or splitting off of the antigens from the cell membrane is mediated by proteases . In the interstitium, the released antigens - also known as shed antigens - surround the tumor cells. But they can also get into the bloodstream via the capillaries . Both of these lead to the fact that antibodies - the opponents of the antigens - and T lymphocytes of the immune system bind to these free antigens without being able to trigger an effect on the target cell. The same applies to antibodies, antibody fragments or antibody mimetics administered as part of cancer immunotherapy . The free antigens thus cause immunosuppression . Antigen shedding is an immune escape mechanism used to evade the immune system.

An example of an antigen released by tumor cells is mesothelin , which is overexpressed in adenocarcinomas , for example . Antigen shedding is a common property of malignant tumor cells.

In many cases, the released antigens can be used as tumor markers in diagnostics .

An opposite effect to antigen shedding, but with similar effects, is antigen masking . Here the antigens on the cell membrane are covered (masked) by polysaccharides and cannot be marked by antibodies or recognized by T lymphocytes. This, too, is an immune escape mechanism of tumor cells.

Individual evidence

  1. ↑ a b c Y. Zhang and I. Pastan: High Shed Antigen Levels within Tumors: An Additional Barrier to Immunoconjugate Therapy. In: Clin Cancer Res 14, 2008, pp. 7981-7986. PMID 19088013 (Review)
  2. ^ SK Law: Antigen shedding and metastasis of tumor cells. In: Clin Exp Immunol 85, 1991, pp. 1-2. PMID 2070554 (review), PMC 1535700 (free full text)
  3. ^ PH Black: Shedding from the cell surface of normal and cancer cells. In: Adr Cancer Res 32, 1980, pp. 75-199. PMID 7008543 (Review)

literature

  • P. Gopalkrishna et al .: Stress induced shedding of a tumor antigen by a rat histiocytic cell line AK-5: a possible mechanism of immune evasion. In: Cell Mol Biol 44, 1998, pp. 563-569. PMID 9678890
  • M. Ferencík and others: Dictionary of Allergology and Immunology. Springer, 2005, ISBN 3-211-20151-3 , p. 30
  • M. Magerstadt: Antibody Conjugates and Malignant Disease. CRC Press, 1991, ISBN 0-849-36089-7