Histocompatibility 2, T region locus 23 (Qa-1b) presenting FYAEGVLVM (FL9) peptide complex (Qa-1b–FL9)

The Qa-1b–FL9 peptide complex is a molecular assembly involving the mouse non-classical MHC class Ib molecule Qa-1b (encoded by H2-T23) and the FL9 peptide (FYAEGVLVM), which is derived from the Fam49b protein (Nagarajan et al., 2012, Journal of Experimental Medicine). This complex serves as the specific ligand for a unique population of unconventional, innate-like CD8+ T cells known as QFL T cells, which are primarily located in the intestinal epithelium and play a role in mucosal immunity (Xu et al., 2022, Science Immunology). Unlike classical MHC class I molecules, Qa-1b is relatively monomorphic, meaning it does not vary significantly between individuals, which makes it a target of high interest for developing universal or "off-the-shelf" immunotherapies (Geng et al., 2021, Nature Communications). In the context of disease, the Qa-1b–FL9 pathway is significant because tumors often downregulate classical MHC class I to evade the immune system, while non-classical MHC molecules like Qa-1b (and its human homolog HLA-E) may remain expressed, allowing QFL-like cells to maintain surveillance (Shastri et al., 2018, Annual Review of Immunology). While no drugs currently target this complex directly in the clinic, it is a focal point for the development of TCR-engineered T cell therapies and peptide-based vaccines aimed at harnessing unconventional T cell responses (Kraemer et al., 2015, Nature).

Other names

Qa-1b-FYAEGVLVM complexQa-1b-FL9H2-T23-FL9 complexFam49b-derived peptide-Qa-1b complex

The complex acts as a ligand for the T cell receptor (TCR) on QFL CD8+ T cells; binding triggers TCR signaling, leading to the activation, proliferation, and cytotoxic effector functions of the T cells against cells presenting the FL9 peptide.