T CELL RECEPTOR.pptx

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1. T CELL RECEPTOR By: D r S adaf M oeez

2. is a protein complex found on the surface of  T cells, or T lymphocytes. R esponsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC ) molecules . The TCR is a member of the immunoglobulin superfamily, a large group of proteins involved in binding, recognition, and adhesion   T CELL RECEPTOR The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules.

3. STRUCTURE OF T CELL RECEPTOR alpha (α) chain and a beta (β) chain are encoded by  TRA  and  TRB , respectively 5% of T cells the TCR consists of gamma and delta (γ/δ) chains (encoded by  TRG  and  TRD ) 95% consists alpha (α) chain and a beta (β) chain

4. STRUCTURE OF T CELL RECEPTOR 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 .

5. The variable domain of both the TCR α-chain and β-chain each have three hypervariable or complementarity-determining regions (CDRs ).

6.   CDR3 is the main CDR responsible for recognizing processed antigen Complementarity-Determining Regions (CDRs) Complementarity-determining regions  (CDRs) are part of the variable chains in immunoglobulins (antibodies) and T cell receptors, generated by B-cells and T-cells respectively

7. STRUCTURE OF T CELL RECEPTOR The constant domain of the TCR consists of short connecting sequences in which a cysteine residue forms disulfide bonds, which form a link between the two chains.

8. TCR is closely associated with the group of adaptor proteins collectively called   TCR COMPLEX ( octameric complex) The complex consists of  both α and β chains, forming the ligand-binding site T he signaling modules: a CD3 γ chain a CD3 δ chain two CD3 ε chains. These chains are associated with the ζ chain (zeta chain). Together those are considered relevant for the transmission of the activation signals for T lymphocytes after peptide binding TCR AND CD3 COMPLEX

9. Generation of the TCR diversity It arises mainly from genetic recombination of the DNA-encoded segments in individual somatic T cells by somatic V(D)J recombination using RAG1 and RAG2  recombinases . The TCR  alpha chain  is generated by VJ recombination The   beta chain  is generated by VDJ recombination

10. During  thymocyte  development, the T cell receptor (TCR) chains undergo essentially the same sequence of ordered recombination events as that described for immunoglobulins . D-to-J recombination occurs first in the β-chain of the TCR. This process can involve either the joining of the D β 1 gene segment to one of six J β 1 segments or the joining of the D β 2 gene segment to one of six J β 2 segments. DJ recombination is followed (as above) with V β -to-D β J β  rearrangements. All gene segments between the V β -D β -J β  gene segments in the newly formed complex are deleted and the primary transcript is synthesized that incorporates the constant domain gene (V β -D β -J β -C β ). mRNA transcription splices out any intervening sequence and allows translation of the full length protein for the TCR β-chain. The rearrangement of the alpha (α) chain of the TCR follows β chain rearrangement, and resembles V-to-J rearrangement described for Ig light chains (see above). The assembly of the β- and α- chains results in formation of the αβ-TCR that is expressed on a majority of T cells.