Discovery of invariant T cells by next generation sequencing of the human T cell receptor α chain repertoire
van Schaik, B., Klarenbeek, P., Doorenspleet, M. et al.
During infection and autoimmune disease, activation and expansion of T cells takes place. Consequently, the T cell receptor (TCR) repertoire contains information about ongoing and past diseases. Analysis and interpretation of the human TCR repertoire is hampered by its size and stochastic variation and by the diversity of antigens and antigen presenting molecules encoded by the Major Histocompatibility Complex (MHC), but is highly desirable and would greatly impact fundamental and clinical immunology. A subset of the TCR repertoire is formed by invariant T cells. Invariant T cells express interdonor-conserved TCRs and recognize a limited set of antigens, presented by non-polymorphic antigen presenting molecules. Discovery of the three known invariant T cell populations has been a tedious and slow process, identifying them one by one. Because conservation of the TCR α chain of invariant T cells is much higher than the β chain, and because the TCR α chain variable (V) gene segment TRAV1-2 is used by two of the three known invariant TCRs, we employed next generation sequencing of TCR α chains that contain the TRAV1-2 gene segment to identify 16 invariant TCRs shared among many blood donors. Frequency analysis of individual clones indicates these T cells are expanded in many donors, implying an important role in human immunity. This approach extends the number of known interdonor-conserved TCRs, suggests that many more exist, and that these TCR patterns can be used to systematically evaluate human antigen exposure.
van Schaik, B., Klarenbeek, P., Doorenspleet, M. et al. "Discovery of invariant T cells by next generation sequencing of the human T cell receptor α chain repertoire" Journal of Immunology (2014): 5,338–44