| First Author | Goodall KJ | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 10 | Pages | 3239-3246 |
| PubMed ID | 31992596 | Mgi Jnum | J:286542 |
| Mgi Id | MGI:6401245 | Doi | 10.1074/jbc.RA119.010509 |
| Citation | Goodall KJ, et al. (2020) The murine CD94/NKG2 ligand, Qa-1(b), is a high-affinity, functional ligand for the CD8alphaalpha homodimer. J Biol Chem 295(10):3239-3246 |
| abstractText | The immune co-receptor CD8 molecule (CD8) has two subunits, CD8alpha and CD8beta, which can assemble into homo or heterodimers. Nonclassical (class-Ib) major histocompatibility complex (MHC) molecules (MHC-Ibs) have recently been identified as ligands for the CD8alphaalpha homodimer. This was demonstrated by the observation that histocompatibility 2, Q region locus 10 (H2-Q10) is a high-affinity ligand for CD8alphaalpha which also binds the MHC-Ib molecule H2-TL. This suggests that MHC-Ib proteins may be an extended source of CD8alphaalpha ligands. Expression of H2-T3/TL and H2-Q10 is restricted to the small intestine and liver, respectively, yet CD8alphaalpha-containing lymphocytes are present more broadly. Therefore, here we sought to determine whether murine CD8alphaalpha binds only to tissue-specific MHC-Ib molecules or also to ubiquitously expressed MHC-Ib molecules. Using recombinant proteins and surface plasmon resonance-based binding assays, we show that the MHC-Ib family furnishes multiple binding partners for murine CD8alphaalpha, including H2-T22 and the CD94/NKG2-A/B-activating NK receptor (NKG2) ligand Qa-1(b) We also demonstrate a hierarchy among MHC-Ib proteins with respect to CD8alphaalpha binding, in which Qa-1(b) > H2-Q10 > TL. Finally, we provide evidence that Qa-1(b) is a functional ligand for CD8alphaalpha, distinguishing it from its human homologue MHC class I antigen E (HLA-E). These findings provide additional clues as to how CD8alphaalpha-expressing cells are controlled in different tissues. They also highlight an unexpected immunological divergence of Qa-1(b)/HLA-E function, indicating the need for more robust studies of murine MHC-Ib proteins as models for human disease. |
