The murine CD94/NKG2 ligand, Qa-1b, is a high-affinity, functional ligand for the CD8αα homodimer
Katharine J. Goodall, Angela Nguyen, Craig I. McKenzie, Sidonia B. G. Eckle, Lucy C. Sullivan, Daniel M. Andrews
Abstract
The immune co-receptor CD8 molecule (CD8) has two subunits, CD8 and CD8, 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 CD8 homodimer. This was demonstrated by the observation that histocompatibility 2, Q region locus 10 (H2-Q10) is a high-affinity ligand for CD8 which also binds the MHC-Ib molecule H2-TL. This suggests that MHC-Ib proteins may be an extended source of CD8 ligands. Expression of H2-T3/TL and H2-Q10 is restricted to the small intestine and liver, respectively, yet CD8-containing lymphocytes are present more broadly. Therefore, here we sought to determine whether murine CD8 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 CD8, 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 CD8 binding, in which Qa-1 b > H2-Q10 > TL. Finally, we provide evidence that Qa-1 b is a functional ligand for CD8, distinguishing it from its human homologue MHC class I antigen E (HLA-E). These findings provide additional clues as to how CD8-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.