Global InformationMHC restriction information
MHC-restricted antigen recognition, or MHC restriction, refers to the fact that a T cell can interact with a self-major histocompatibility complex molecule and a foreign peptide bound to it, but will only respond to the antigen when it is bound to a particular MHC molecule.[1]
When foreign proteins enter a cell, they are broken into smaller pieces called peptides. These peptides, also known as antigens, can derive from pathogens such as viruses or intracellular bacteria. Foreign peptides are brought to the surface of the cell and presented to T cells by proteins called the major histocompatibility complex (MHC). During T cell development, T cells go through a selection process in the thymus to ensure that the T cell receptor (TCR) will not recognize MHC molecule presenting self-antigens, i.e that its affinity is not too high. High affinity means it will be autoreactive, but no affinity means it will not bind strongly enough to the MHC. The selection process results in developed T cells with specific TCRs that might only respond to certain MHC molecules but not others. The fact that the TCR will recognize only some MHC molecules but not others contributes to "MHC restriction". The biological reason of MHC restriction is to prevent supernumerary wandering lymphocytes generation, hence energy saving and economy of cell-building materials. [2]
T-cells are a type of lymphocyte that is significant in the immune system to activate other immune cells. T-cells will recognize foreign peptides through T-cell receptors (TCRs) on the surface of the T cells, and then perform different roles depending on the type of T cell they are in order to defend the host from the foreign peptide, which may have come from pathogens like bacteria, viruses or parasites. Enforcing the restriction that T cells are activated by peptide antigens only when the antigens are bound to self-MHC molecules, MHC restriction adds another dimension to the specificity of T cell receptors so that an antigen is recognized only as peptide-MHC complexes.[3]
MHC restriction in T cells occurs during their development in the thymus, specifically positive selection.[4] Only the thymocytes (developing T cells in the thymus) that are capable of binding, with an appropriate affinity, with the MHC molecules can receive a survival signal and go on to the next level of selection. MHC restriction is significant for T cells to function properly when it leaves the thymus because it allows T cell receptors to bind to MHC and detect cells that are infected by intracellular pathogens, viral proteins and bearing genetic defects. Two models explaining how restriction arose are the germline model and the selection model.
The germline model suggests that MHC restriction is a result of evolutionary pressure favoring T cell receptors that are capable of binding to MHC.[5] The selection model suggests that not all T cell receptors show MHC restriction, however only the T cell receptors with MHC restriction are expressed after thymus selection.[6] In fact, both hypotheses are reflected in the determination of TCR restriction, such that both germline-encoded interactions between TCR and MHC and co-receptor interactions with CD4 or CD8 to signal T cell maturation occur during selection.[7]
- ^ Immunobiology: The Immune System in Health and Disease. 5th edition. Janeway CA Jr, Travers P, Walport M, et al. New York: Garland Science; 2001. https://www.ncbi.nlm.nih.gov/books/NBK10757/
- ^ Nesmiyanov, P (2020). "Antigen Presentation and Major Histocompatibility Complex". Reference Module in Biomedical Sciences: 90–98. doi:10.1016/B978-0-12-818731-9.00029-X. ISBN 9780128012383. S2CID 234948691.
- ^ Charles A Janeway, Jr; Travers, Paul; Walport, Mark; Shlomchik, Mark J. (2001-01-01). "Antigen Recognition by B-cell and T-cell Receptors". Garland Science.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Van Laethem, François; Tikhonova, Anastasia N.; Singer, Alfred (2012-01-09). "MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection". Trends in Immunology. 33 (9): 437–441. doi:10.1016/j.it.2012.05.006. ISSN 1471-4906. PMC 3427466. PMID 22771139.
- ^ Christopher Garcia, K; Adams, Jarrett J; Feng, Dan; Ely, Lauren K (2009-01-16). "The molecular basis of TCR germline bias for MHC is surprisingly simple". Nature Immunology. 10 (2): 143–147. doi:10.1038/ni.f.219. PMC 3982143. PMID 19148199.
- ^ Collins, Edward J.; Riddle, David S. (2008-08-26). "TCR-MHC docking orientation: natural selection, or thymic selection?". Immunologic Research. 41 (3): 267–294. doi:10.1007/s12026-008-8040-2. ISSN 0257-277X. PMID 18726714. S2CID 33347746.
- ^ Garcia, K. Christopher (2012-09-01). "Reconciling views on T cell receptor germline bias for MHC". Trends in Immunology. 33 (9): 429–436. doi:10.1016/j.it.2012.05.005. PMC 3983780. PMID 22771140.