Doubting the TCR coreceptor function of CD8αα

The beginning of wisdom is found in doubting; by doubting we come to question, and by seeking we may come upon the truth. - Pierre Abelard CD8 is a glycoprotein expressed on hematopoietic cells. Two isoforms of CD8, CD8 alpha beta and CD8 alpha alpha, have been identified that are distinct in their expression and function. Whereas CD8 alpha beta serves as a T cell receptor (TCR) coreceptor to enhance the functional avidity and is constitutively expressed on MHC class I-restricted T cells, CD8 alpha alpha marks T cells that are distinct from the conventional thymus-selected and MHC-restricted CD4(+) or CD8 alpha beta(+) T cells. Inconsistent with a coreceptor function, CD8 alpha alpha decreases antigen sensitivity of the TCR, and it can be transiently or permanently expressed on T cells, regardless of the MHC restriction of the TCR or the presence of conventional coreceptors. Together, these observations indicate that CD8 alpha alpha on T cells marks a differentiation stage and that it likely functions as a TCR corepressor to negatively regulate T cell activation.