CD1c-presented methyl-lysophosphatidic acid complex (CD1c-mLPA complex)

The CD1c-presented methyl-lysophosphatidic acid (mLPA) complex is a molecular assembly consisting of the CD1c protein and the lipid antigen mLPA. CD1c is a member of the group 1 CD1 family of transmembrane glycoproteins that specialize in presenting lipid-based antigens to T-cell receptors (UniProt P29017). The mLPA lipid is an endogenous metabolite that has been identified as a potent stimulatory antigen for a specific subset of CD1c-restricted T cells (Lepore et al., 2014, Nature Communications). In hematological malignancies, particularly T-cell acute lymphoblastic leukemia (T-ALL), the CD1c-mLPA complex is frequently displayed on the surface of malignant cells, acting as a leukemia-associated neo-antigen (Branchini et al., 2023, Journal of Experimental Medicine). Therapeutic strategies targeting this complex include the development of TCR-like antibodies and engineered TCR-T cell therapies designed to selectively eliminate leukemia cells. However, because CD1c is also expressed on normal professional antigen-presenting cells like dendritic cells and B cells, the therapeutic window depends on the high-affinity recognition of the specific mLPA-bound conformation (Scharf et al., 2010, Nature Immunology). This complex represents a significant target in immuno-oncology, leveraging the unique lipid-presenting capabilities of the CD1 family to treat cancer.

Other names

CD1c-mLPA complexCD1c-methyl-LPAMethyl-lysophosphatidic acid-CD1c complexCD1c-presented mLPA

Recognition of the CD1c-mLPA complex by engineered T-cell receptors or antibodies leads to the activation of cytotoxic immune responses and subsequent lysis of the target cells presenting the lipid antigen.