Fig. 1: Schematic representation of T cell development in the thymus.

Bone marrow derived lymphoid progenitor cells (CD4-CD8- double negative, DN) first enter the thymus from the corticomedullary junction region and migrate towards the outer cortex where differention from stages DN1 to DN4 take place. At the DN3 stage, cells expressing TCRβ chain genes continue to develop as αβ lineage cells and later express pTCRα which is needed for development of a diverse TCR repertoire and progression to CD4+CD8+ double positive (DP) thymocytes. The cells next undergo positive and negative selection, where interaction with peptide-MHC complexes triggers the enrichment of those that are potentially reactive to foreign antigens. Thymocytes that have been positively selected proceed to differentiate into CD4+ or CD8+ single positive (SP) cells and migrate to the medulla and achieve central tolerance, before export to the periphery. Notably, cells lacking the TCRβ chain at the DN3 stage, instead expressing TCRγ and TCRδ genes, are exported to the periphery as γδ lineage T cells. Aberrations in PTCRA resulting in loss of pTCRα expression leads to reduced αβ lineage T cells and increased γδ T cell populations. Schematic was prepared using Canva.