CD8αα and CD8αβ: truly different?

CD8 is a coreceptor of T cells for the recognition of peptide–MHC (pMHC) on antigen-presenting cells. It exists in two forms: an αα homodimer and an αβ heterodimer. The different functions of these two forms have long been a mystery, although it is believed that the heterodimer has a stronger affinity than the homodimer for pMHC. The structural basis of the interaction between pMHC and the αα homodimer in humans and mice was determined by X-ray crystallography a few years ago, but no structural explanation for the functional differences between homo- and heterodimers could be deduced. Two recent papers provide some clues on this matter.