Human Leukocyte Antigen (HLA) part 42

HLA and selection in thymus

T cells arise from circulating bone-marrow-derived progenitors that home to the thymus. After T lineage commitment and expansion, T cell receptor gene rearrangement ensues and give rise to either γδ or αβ progenitors at the CD4 and CD8 double-negative stage. A small number of  αβ committed double-negative  cells give rise to a large number of CD4 and CD8 double-positive thymocytes, and somatic recombination of T cell receptors genes result in a remarkably broad repertoir of distinc αβ T cell receptor with random specificity. The T cell receptor  affinity for self-peptide-HLA determines a thymocyte's fate from this point forward.   Double positive thymocyte  expressing T cell receptors that do not bind  self-peptide-HLA complexes die by neglect. Those with low affinity for self-peptide-HLA  complexes differentiate to CD4 or CD8 single-positive thymocytes - so called positive selection.  However, those with high-affinity T cell receptor  for self-peptide-HLA complexes represent a potential threat to the health, and various  mechanisms operate to ensure  tolerance to self, including clonal deletion, clonal diversion, receptor editing and anergy