T - CELL RECEPTOR The T cell receptor or TCR is a complex of integral membrane proteins found on the surface of T lymphocytes (or

T cells) that participates in the activation of T-Cells by recognizing antigens presented by major histocompatibility complex (MHC) molecules. Engagement of the TCR initiates positive and negative cascades that ultimately result in cellular proliferation, differentiation, Cytokine production, and/or activation-induced cell death. There are two types of TCRs, the predominant which is commonly found in lymphoid tissues, and the which is found at mucosal surfaces. 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 () and beta () chain, whereas in 5% of T cells this consists of gamma and delta (/) chains.

Structure of TCR
TCR, which is anchored in the cell membrane, consists of two halves, which form a pair (or dimer) of protein chains. The halves are called the alpha () and beta () fragments (in / T cells, the halves are gamma () and delta () fragments). Each fragment is divided in turn into a constant (C) and variable (V) region. The constant region has an end that is anchored in the cell membrane. The variable region faces outward and binds to the HLA molecule and the antigen it presents. On the chain, the variable region is called V and the constant region is called C; on the chain, they are called V and C, respectively. The structure of TCR is very similar to immunoglobulin Fab fragments, which are regions defined as the combined light and heavy chain of an antibody arm. Each chain of the TCR is a member of the immunoglobulin superfamily and possesses one N-terminal immunoglobulin (Ig)variable (V) domain, one Ig-constant (C) domain, a transmembrane/cell membrane-spanning region, and a short cytoplasmic tail at the C-terminal end. The variable domain of both the TCR -chain and -chain have three hypervariable or complementarity determining regions (CDRs), whereas the variable region of the -chain has an additional area of hypervariability (HV4) that does not normally contact antigen and, therefore, is not considered a CDR. 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 -chain interacts with the C-terminal part of the peptide. 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 Processes for TCR formation are similar to those described for B cell antigen receptors, otherwise known as immunoglobulins. The TCR alpha chain is generated by VJ recombination, whereas the beta chain is generated by V(D)J recombination (both involve 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 V(D)J 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 antigen-MHC recognition.

Function of the TCR Involves in the activation of T-Cells. Recognizes the antigens presented by major histocompatibility complex (MHC) molecules. Engagement of the TCR initiates positive and negative cascades that ultimately result in cellular proliferation, differentiation, Cytokine production, and/or activation-induced cell death.

CD3: Synthesized coordinately with TCR which is required to bring TCR to surface and transduces activating signals to T cell when TCR recognizes MHC-peptide.