T-cell receptor (TCR) is a protein complex on T cells' surface responsible for antigen recognition. The receptor allows antigens bound to the major histocompatibility complex (MHC) molecules expressed on antigen-presenting cells (APC) to be recognized. This specific recognition is vital in the cellular immune response. The complex is a membrane-anchored and disulfide-linked heterodimeric set of glycoproteins with about 95% consisting of an alpha-beta chain (TCRαβ) and 5% gamma-delta (TCRγδ) chains. The prevalent αβ chains consist of two extracellular domains, the variable (V) and constant (C) region, with the C region adjacent to the cell membrane, the transmembrane domain and a short cytoplasmic tail and the V region bonded to the MHC complex and a cysteine-containing sequence. TCRα is specifically of major interest in this study, as it contains sites with increased amino acid variability present in its V domain. These complementarity-determining regions (CDRs) determine specific antibody binding to the receptors and includes CDR1, CDR2, CDR3 and HV4 involved in pMHC (Peptide-bound MHC) recognition. Initiation of specific mutations in these domains ensures efficient protection against pathogens and the generation of an immune response. We will present our work on the expression and purification of TCRα and initial structural characterization using NMR. A study of the structure and dynamics of these transmembrane domains will give a better structural and functional understanding of the TCRα and TCR complex.

Recombinant Expression and Characterization of TCRa from the T-cell Receptor Complex