Meet Inspiring Speakers and Experts at our 3000+ Global Conferenceseries Events with over 1000+ Conferences, 1000+ Symposiums and 1000+ Workshops on Medical, Pharma, Engineering, Science, Technology and Business.
Explore and learn more about Conference Series Ltd: World’s leading Event Organizer
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes (or T cells) that is responsible for recognizing antigens bound to major histocompatibility complex (MHC) molecules. The binding between TCR and antigen is of relatively low affinity and is degenerate: that is, many TCR recognize the same antigen and many antigens are recognized by the same TCR. The TCR is composed of two different protein chains (that is, it is a heterodimer). In 95% of T cells, this consists of an alpha (α) and beta (β) chain, whereas in 5% of T cells this consists of gamma and delta (γ/δ) chains. This ratio changes during ontogeny and in diseased states. When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors.
The TCR is a disulfide-linked membrane-anchored heterodimer normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. T cells expressing this receptor are referred to as α:β (or αβ) T cells, though a minority of T cells express an alternate receptor, formed by variable gamma (γ) and delta (δ) chains, referred as γδ T cells. Each chain is composed of two extracellular domains: Variable (V) region and a Constant (C) region, both of Immunoglobulin superfamily (IgSF) domain forming antiparallel β-sheets. The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail, while the Variable region binds to the peptide/MHC complex.The variable domain of both the TCR α-chain and β-chain each have three hypervariable or complementarity determining regions (CDRs), whereas the variable region of the β-chain has an additional area of hypervariability (HV4) that does not normally contact antigen and, therefore, is not considered a CDR.The residues are located in two regions of the TCR, at the interface of the α- and β-chains and in the β-chain framework region that is thought to be in proximity to the CD3 signal-transduction complex. CDR3 is the main CDR responsible for recognizing processed antigen, although CDR1 of the alpha chain has also been shown to interact with the N-terminal part of the antigenic peptide, whereas CDR1 of the β-chain interacts with the C-terminal part of the peptide.CDR2 is thought to recognize the MHC. CDR4 of the β-chain is not thought to participate in antigen recognition, but has been shown to interact with superantigens.The constant domain of the TCR domain consists of short connecting sequences in which a cysteine residue forms disulfide bonds, which forms a link between the two chains.
Generation of the TCR diversity:
Processes for the generation of TCR diversity are similar to those described for B cell antigen receptors, otherwise known as immunoglobulins. It is based mainly on somatic recombination of the DNA encoded segments in individual T cells.
TCRs possess unique antigen specificity, determined by the structure of the antigen-binding site formed by the α and β chains.
• The TCR alpha chain is generated by VJ recombination, whereas the beta chain is generated by VDJ recombination (both involving a somewhat random joining of gene segments to generate the complete TCR chain).
• Likewise, generation of the TCR gamma chain involves VJ recombination, whereas generation of the TCR delta chain occurs by VDJ recombination.
The intersection of these specific regions (V and J for the alpha or gamma chain; V, D, and J for the beta or delta chain) corresponds to the CDR3 region that is important for peptide/MHC recognition (see above).It is the unique combination of the segments at this region, along with palindromic and random nucleotide additions (respectively termed "P-" and "N-"), which accounts for the great diversity in specificity of the T cell receptor for processed antigen.The TCR receptor complex is an octomeric complex of variable TCR receptor α and β chains with three dimeric signaling modules CD3δ/ε, CD3γ/ε and CD247 ζ/ζ or ζ/η. Ionizable residues in the transmembrane domain of each subunit form a polar network of interactions that hold the complex together. Since the cytoplasmic tail of the TCR is extremely short, making it unlikely to participate in signaling, these signaling molecules are vital in propagating the signal from the triggered TCR into the cell.Each T cell express clonal TCR which recognize specific peptide/MHC complex during physical contact between T cell and antigen-presenting cell-APC (MHC class II) or any other cell type (MHC class I) High on-rate and off-rate is characteristic for TCR and peptide/MHC interaction at physiological temperature. TCRs have very high degree of antigen specificity, despite of fact that the affinity to the peptide/MHC ligand is in the micromolar range. This weak binding ( dissociation constant values) between TCR and peptide/MHC was determined by the surface plasmon resonance (SPR) to be in the range 1-100 μM, the association constant in the range from 1000 to 10000 M−1×s−1, The TCR affinity for peptided/MHC has a direct impact on modulation of T cell function. T cell are very sensitive to their antigens despite the low affinity of TCR for its peptide/MHC and low numbers of specific peptide/MHC and the surface of target cells. The specific and efficient signaling via TCR might be regulated by dynamic oligomerization into TCR microclusters on the surface of T cell. In this scenario, T cell sensitivity to antigen could be increased via avidity-based mechanism. The antigen sensitivity is higher in antigen-experienced T cells than in naive T cells. Naive T cells pass through the process of functional avidity maturation with no change in affinity. It is based on fact that effector amd memory (antigen-experienced) T cell are less dependent on costimulatory signals and higher antigen concentration than naive T cell. The essential function of the TCR complex is to identify specific bound antigen and elicit a distinct and critical response. The mechanism by which a T-cell elicits this response upon contact with its unique antigen is termed T-cell activation. There are myriad molecules involved in the complex biochemical process (called trans-membrane signalling) by which this occurs.The most common mechanism for activation and regulation of molecules beneath the lipid bilayer is via phosphorylation/dephosphorylation by protein kinases. T-cells utilise the Src family kinases in transmembrane signalling largely to phosphorylate tyrosines that are part of immunoreceptor tyrosine-based activation motifs (ITAM) in intracellular parts of CD3 and ζ chains.
Early signaling steps implicate the following kinases and phosphatases after TCR triggering:
• Lck – Src family kinase associated with the intracellular tail of CD4 and phosphorylate ITAMs
• Fyn – Src family kinase phosphorylate ITAMs of the CD3 and ζ ITAMs of the TCR complex
• CD45 – The intracellular tail function as a tyrosine phosphatase activating Src family kinases
• Zap70 – Syk family kinase bind to ITAM sequences upon tyrosine phosphorylation by Lck and Fyn and phosphorylate LAT
When a T cell receptor is activated by contact with a peptide:MHC complex, CD45 dephosphorylates inhibitory tyrosine of membrane-localized Src family kinases Fyn and Lck, previously recruited and activated by CD4 or CD8 coreceptors. Activated Fyn and Lck phosphorylates ITAMs on the CD3 and ζ chains. This allows cytoplasmic kinases of the Syk family (ZAP-70) to bind to the ITAM and activated ZAP-70 phosphorylates tyrosines on the adaptor protein LAT, which then attracts PLC-γ. Other downstream pathways are triggered as well (MAPK, NF-κB, NFAT) which results in gene transcription in the nucleus.
OMICS Group, the top Open access publisher and best International conference organizer liaise with various organizations, universities, media schools and individual expert personnel to ensure their work publication and exploration in more than 300 leading edge peer-reviewed Open Access journals and hosts over 100 scientific conferences all over the world. OMICS Group adds a fruitful contribution to the world community providing a free access to the highly accredited work and related high profiled eminent. OMICS Group is a global network comprising of different communities with a team of more than 30,000 contributing members from various fields and still boasting a base to inter connect the overseas knowledge of more than 5 million followers. OMICS Group International is providing an international platform for the various renowned personalities, top executors, eminent producers, directors, acting schools, entrepreneurs and industries by hosting the best academic conferences all over the world. These international conferences offer a perfect stage for the expertise from across the globe to share and explore the recent advancements in the field during the interactive scientific sessions, symposiums, poster presentations and workshops.OMICS Group International ventured into Scientific Alliance, has already signed agreement with more than 1000 scientific associations worldwide to make health care and scientific information open access. This brings together a platform for global networking among the community through shared resources and working together in multifarious key areas. Now OMICS Group is going to organize International conference on Thrombosis and hemostasis in Beijing, China on July 13-15, 2015.
1. 3rd International Conference and Exhibition on Clinical & Cellular Immunology
2. Advances in Cancer Immunotherapy
3. SITC 2014 Primer on Tumor Immunology and Cancer Immunotherapy
4. British Society for Immunology annual conference December 1-4 Brighton Uk 5. Immunology International Conference
1. The American Association of Immunologists
2. The American Academy of Allergy Asthma and Immunology
3. British Society for Immunology
4. The Association of Medical Laboratory Immunologists
5. European Academy of Allergology and Clinical Immunology Organisation
6. Norwegian Society for Immunology
7. International Union of Immunological Societies
8. Federation of Clinical Immunology Societies
9. Canadian Society for Immunology
10. Canadian Society of Allergy and Clinical Immunology
1. Cellectis France
2. Immunocore Limited UK
3. ImmunID France
4. Midwest Allergy Asthma and Immunology Associates USA
5. Applied Immunology USA
6. Pacific Immunology USA
7. Miltenyi Biotec USA
8. Whitehead Institute USA
9. Gladstone Institutes USA
10. Genova Diagnostics USA
This page will be updated regularly.
This page was last updated on 10th Oct, 2014
1-702-508-5200 Ext:8031, 8041
1-702-508-5200 Ext:8045, 8047
Immunology & Microbiology Conferences
Nursing and Healthcare Conferences
Clinical and Biochemistry Conferences
1-702-508-5200 Ext:8031, 8037
Material Science Conferences
Genetics & Mol Biology Conferences
Media Partners | Advertising