CD4+ T cells, also known as helper T cells (Th cells), support B and T cell immune responses (more on helper T cells). Once activated, Th cells differentiate into different effectors, depending on chemical factors in the local environment, called cytokines. One of these effectors is Th1, mainly involved in an antiviral response or response combating intracellular pathogens. After the antigen has been cleared from the system, most of the Th1 cells are eliminated by immune system controls, however, a small number of the Th1 cells survive and differentiate into memory T cells. Although the process in which Th cells differentiate into Th1 cells has been extensively studied, very little is known about the differentiation of Th1 cells into memory cells! Knowing the steps involved in memory cell differentiation is important, because not only do they indicate the factors that effect T cell fate, but this knowledge could be used to design better vaccines that are aimed at increasing memory T cell formation! T cell receptors (TCRs) (more on T cells and TCRs) create signals during activation that impact the differentiation and expansion of the T cell, therefore, there is a possibility that TCR signaling determines the end fate of T cells as well: whether they become long-lived memory T cells or end-stage effectors to be eliminated after the pathogen has been cleared.
In a recent study, Kim et al investigated the impact of TCR signals on the end fate of Th1 cells. They determined which TCR-binding characteristics correspond to memory differentiation. To do this, they cloned TCR sequences obtained in a deep sequencing process, and then they transfected 293 T cells with TCR retroviral expression vectors so they could express these TCRs. Next, the T cells were infected with GP 66-77 tetramer (an antigen glycoprotein), and the tetramer off rates (the rate at which TCR and pMHC dissociate) and avidity (number of TCR-pMHC interactions occurring) for TCRs were measured. Some TCRs had high avidity with quick off rates, and some had low avidity with extremely slow off rates. When compared to TCR survival 8-42 days after infection, the only significant predictor of memory T cell potential was the tetramer off rate.