How do T cells develop?
T-cell precursors from the bone marrow enter the thymus where they begin the process of becoming a naïve T cell. Nearly 99% of cells die in this process.
First, cells undergo positive selection in which the T cell must generate a TCR that, along with either CD4 or CD8, is capable of seeing antigen presented by MHC. The majority of circulating lymphocytes in the bloodstream are T cells with a TCR comprising an α-chain and a β-chain. To generate diversity, the TCR β-chain genes on chromosome 7 contain four segments (V, D, J, C), whereas the α-chain genes on chromosome 14 contain three segments (V, D, C). Each segment has several members to choose from (50-100V, 15D, 6-60 J, 1-2 C) in a process called gene recombination in which the T cell selects to use only one of each of these segments. This process of TCR gene rearrangement and the combination of the two TCR chains yield >10 8 possible combinations. After generating a TCR successfully, the T cell undergoes negative selection. In this case, T cells that bind too strongly to self-antigen or MHC and those that do not bind at all are eliminated.
T cells that survive the processes in the thymus are then released as naïve T cells into circulation where they will traffic to secondary lymphoid tissues to mature and differentiate.