T cell receptor complex and diversity Semester : III Course Title : Immunology Unit : III Staff In-Charge : Prof.T.Antony Diwakar Chandran

T-Cell Receptor Complex: TCR-CD3

The first evidence suggesting that the T-cell receptor is associated with another membrane molecule came from experiments in which fluorescent antibody to the receptor was shown to cause aggregation of another membrane protein designated CD3. CD3 is a complex of five invariant polypeptide chains that associate to form three dimers: a heterodimer of gamma and epsilon chains (γε), a heterodimer of delta and epsilon chains (δε), and a homodimer of two zeta chains (ζζ) or a heterodimer of zeta and eta chains (ζη) The ζη and chains are encoded by the same gene, but differ in their carboxyl-terminal ends because of differences in RNA splicing of the primary transcript.About 90% of the CD3 complexes examined to date incorporate the (ζζ) homodimer; the remainder have the (ζη) heterodimer. The T-cell receptor complex can thus be envisioned as four dimers: the or TCR heterodimer determines the ligand-binding specificity, whereas the CD3 dimers (, , and or ) are required for membrane expression of the T-cell receptor and for signal transduction.

T-Cell Accessory Membrane Molecules CD4 and CD8 Coreceptors Bind to Conserved Regions of MHC Class II or I Molecules. CD4 is a 55-kDa monomeric membrane glycoprotein that contains four extracellular immunoglobulin-like domains (D1–D4), a hydrophobic transmembrane region, and a long cytoplasmic tail containing three serine residues that can be phosphorylated. CD8 generally takes the form of a disulfidelinked heterodimer or of an homodimer. Both the and chains of CD8 are small glycoproteins of approximately 30–38 kDa. Each chain consists of a single extracellular immunoglobulin-like domain, a hydrophobic transmembrane region, and a cytoplasmic tail containing 25–27 residues, several of which can be phosphorylated.

Affinity of TCR for Peptide-MHC Complexes Is Weak Compared with Antibody Binding

As in the case of Ig genes, functional TCR genes are produced by rearrangements of V and J segments in the alpha -chain and gamma- chain families and V, D, and J segments in the delta-chain and beta-chain families. The -gene segments are located on chromosome 14 between the V and J segments. The location of the –chain gene family is significant: a productive rearrangement of the -chain gene segments deletes C, so that, in a given T cell, the TCR receptor cannot be coexpressed with the receptor.

Rearranged TCR Genes Are Assembled from V, J, and D Gene Segments TCR Diversity Is Generated Like Antibody Diversity but Without Somatic Mutation