A conformation- and avidity-based proofreading mechanism for the TCR-CD3 complex

Trends in Immunology
Wolfgang W A SchamelBalbino Alarcón

Abstract

During antigen recognition, T cells show high sensitivity and specificity, and a wide dynamic range. Paradoxically, these characteristics are based on low-affinity receptor-ligand interactions [between the T-cell antigen receptor (TCR-CD3) complex and the antigen peptide bound to MHC]. Recent evidence indicates that the TCR-CD3 is expressed as multivalent complexes in the membrane of non-stimulated T cells and that conformational changes in the TCR-CD3 can be induced by strong but not weak agonists. Here, we propose a thermodynamic model whereby the specificity of the TCR-CD3-pMHC interaction is explained by its multivalent nature. We also propose that the free energy barriers involved in the change in conformation of the receptor impose a response threshold and determine the kinetic properties of recognition. Finally, we suggest that multivalent TCR-CD3s can amplify signals by spreading them from pMHC-engaged TCR-CD3s to unengaged complexes as a consequence of the cooperativity in the system.

References

Aug 1, 1995·Molecular Immunology·M ExleyC Terhorst
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·T W McKeithan
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·K MatsuiM M Davis
Nov 1, 1994·Molecular Immunology·R C BrowerC Delisi
May 23, 1998·Annual Review of Immunology·M M DavisY Chien
Apr 5, 2001·Trends in Molecular Medicine·C Soto, G P Saborío
Jun 23, 2001·Immunity·P A van der Merwe
Jan 16, 2002·Current Opinion in Immunology·Markus G Rudolph, Ian A Wilson
Oct 25, 2002·Nature·Darrell J IrvineMark M Davis
Mar 5, 2003·Immunological Reviews·Balbino AlarcónWolfgang W A Schamel
Mar 5, 2003·Annual Review of Immunology·P Anton van der Merwe, Simon J Davis
Mar 30, 2004·Nature Immunology·Marco A PurbhooMark M Davis
Mar 18, 2005·Annual Review of Immunology·Matthew E Call, Kai W Wucherpfennig
Aug 10, 2005·The Journal of Experimental Medicine·Wolfgang W A SchamelBalbino Alarcón
Oct 12, 2005·The Journal of Experimental Medicine·Gabriele CampiMichael L Dustin
Oct 20, 2005·PLoS Biology·Grégoire Altan-Bonnet, Ronald N Germain
Nov 19, 2005·Science·Kaspar D MossmanMichael L Dustin

❮ Previous
Next ❯

Citations

Oct 7, 2008·Cancer Immunology, Immunotherapy : CII·Tamson V MooreMichael I Nishimura
Jul 21, 2006·Nature Immunology·Simon J Davis, P Anton van der Merwe
Jul 25, 2009·The Journal of Biological Chemistry·Kaushik ChoudhuriP Anton van der Merwe
Dec 14, 2007·Molecular Biology of the Cell·Isabel María OlazabalFrancisco Sánchez-Madrid
Nov 10, 2010·International Immunology·Ignacio ArechagaJosé María Valpuesta
Nov 5, 2010·Cold Spring Harbor Perspectives in Biology·Naomi E Harwood, Facundo D Batista
Jun 3, 2010·Cold Spring Harbor Perspectives in Biology·Jesse CowardGrégoire Altan-Bonnet
Mar 3, 2010·Annual Review of Immunology·Naomi E Harwood, Facundo D Batista
Nov 1, 2007·Proceedings of the National Academy of Sciences of the United States of America·John R JamesDavid Klenerman
Jul 18, 2006·Biochemical and Biophysical Research Communications·Peter NagyLászló Damjanovich
Jun 12, 2012·Molecular Immunology·Jun HuangCheng Zhu
Sep 11, 2010·FEBS Letters·Eszter MolnárWolfgang W A Schamel
Jan 19, 2008·Trends in Biochemical Sciences·Susana Minguet, Wolfgang W A Schamel
Jan 22, 2008·Immunology Letters·Susana MinguetWolfgang W A Schamel
Jun 15, 2007·Seminars in Immunology·Kaushik Choudhuri, P Anton van der Merwe
May 4, 2006·EMBO Reports·Balbino AlarcónWolfgang W A Schamel
Feb 20, 2008·Scandinavian Journal of Immunology·M SwamyW W A Schamel
Mar 13, 2012·Journal of Molecular Recognition : JMR·Thomas C NessporRandall J Brezski
Jun 3, 2011·Immunology·Balbino AlarcónNuria Martínez-Martín
Aug 28, 2012·The EMBO Journal·Noa B Martín-CófrecesFrancisco Sánchez-Madrid
Nov 26, 2009·Proteins·David AbiaAnna Tramontano
Nov 3, 2016·Chemical Research in Toxicology·Monday O OgeseDean J Naisbitt
Dec 4, 2010·Nature Reviews. Immunology·P Anton van der Merwe, Omer Dushek
Mar 7, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Diana GilEd Palmer
Aug 22, 2018·Immunological Reviews·Jesús A Siller-Farfán, Omer Dushek
Sep 10, 2020·International Journal of Molecular Sciences·Anastasios SiokisMichael Meyer-Hermann
Oct 31, 2020·International Journal of Molecular Sciences·Elizabeth M KolawoleBrian D Evavold

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.