There are a variety of non-mutually exclusive factors that lead to a fully activated T cell, such as the quantity of peptide-MHC presented on the surface of antigenpresenting cells and TCR avidity. The interaction between the peptide-MHC and TCR is critical for the initiation of an adaptive immune response and clearance of a pathogen [15] . In order for T cells to reach maturity, the T cell goes through a number of developmental checkpoints leading to somatic recombination of various gene segments. The TCR αand β-chains are generated by V-D-J recombination, which leads to αβ TCRs expressed on the surface of T cells [42, 43] . Although it was believed that T cell signaling was mediated by a single antigen receptor, recent evidence demonstrates that T cells are capable of expressing functional dual Vα TCRs at a frequency of approximately 30% in humans and 15% in mice; however, an accurate number of dual specific TCRs is lacking due to the limited availability of anti-Vα monoclonal antibodies (mAbs) [44] [45] [46] . Interestingly, in contrast to the high frequency of dual expressing Vα T cells, only 1% of humans and 5-7% of mice express two β-chains due to allelic exclusion mechanisms, but the frequencies of dual Vβ TCRs have been found to be higher with age and in TCR-tg mice [47] [48] [49] . Expression of multiple TCR Vαs on the surface of a T cell is the result of simultaneous rearrangement of both TCRα loci during thymocyte development [50-52]. Further, TCR Vβ-chains preferentially bind to certain Vαchains leading to differential expression of chimeric TCRs on the surface of T cells [51, 53, 54].