The CD8 isoform CD8αα is not a functional homologue of the TCR co-receptor CD8αβ

Although structurally similar, CD8αβ and CD8αα have notably diverted with regard to function. Whereas CD8αβ functions as a T-cell receptor (TCR) co-receptor on MHC-class-I-restricted thymocytes and mature T cells, CD8αα is unable to support conventional positive selection, and can be expressed on T cells independent of the MHC restriction of their TCR. CD8αα induction is consistent with antigenic stimulation through the TCR, and recent developments have now shown that CD8αα induced on agonist-triggered immature thymocytes, antigenic-stimulated conventional CD8αβ T cells and mucosal T cells mediates the specific modulation of TCR activation signals to facilitate their survival and differentiation into various specialized T-cell subsets.