The thymus-dependent T cell differentiation processes (CD4+T helper cells, CD8+ killer or cytotoxic T cells, and CD4+Tregs) ensure the recognition of foreign Ags in context with the recognition of self-MHC or human leukocyte antigen (HLA) molecules (MHC-I or HLA-1 and MHC-II or HLA-II) expressed on different antigen-presenting cells (APCs, such as DCs, macrophages, and B cells) without inducing self-reactive autoimmunity along with supporting the development of several minor T cell subsets that promote immune and tissue homeostasis (Figure 1) [76]. The gene discussed is CD8A; the disease is Autoimmunity.