CD1C: A Dendritic Cell Surface Marker that Induces T-Cell Response

CD1C belongs to the CD1 family that plays roles in adaptive immunity, tissue homeostasis,and autoimmune diseases. Like MHC class I molecules (MHC-I), CD1 proteins form heterodimers with β2-macroglobulin (B2M) and present lipid antigens on the cell surface to interact with T cells. Human CD1 proteins (CD1A, CD1B, CD1C, CD1D, and CD1E) have different structural frameworks in their ligand-binding pockets, which may result in their different preference for bound lipids. For example, the anti-tumor immunostimulant α-galactosylceramide (α-GalCer) binds CD1D, whereas the cancer lipid antigen methyl-lysophosphatidic acid (LPA) binds CD1C. In addition, CD1 isotypes distribute differently in the cellular endomembrane system.

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CD1 Family

Dendritic Cell Marker

Immune Checkpoint Protein

Surface CD1 proteins engaged by unconventional T cells

TCRS in unconventional T-cells can recognize loaded CD1 on the cell surface. Unconventional T-cells include a compartment of T cell subsets that recognize various non-classical MHC molecules such as CD1 and HLA-E. This group of T cells has developmental patterns different from conventional T cells, such as their early presence in life, the restricted TCR profile (against monomorphic ligands), high frequency in local tissues, and memory-like T cell state (ready for cytokine secretion). Due to these respects, unconventional T cells and their corresponding CD1 ligands, like natural killer T cells (NKT) and CD1D, have been targeted in various clinical trials, including CAR T-cell cancer therapies.

CD1C: A defining marker for dendritic cell subsets

CD1C is widely localized throughout the endocytic system and the plasma membrane of the antigen-presenting cells. CD1C is expressed on the surface of B cells in lymph nodes, spleen, and blood. CD1C expression can also be induced in activated monocytes. Furthermore, CD1C is a defined marker of subsets of conventional dendritic cells (cDC2 and cDC3). cDC2 are recently found able to prime CD4⁺ effector T cells to infiltrate tumors and may serve as a prognostic indicator for survival and response to immune checkpoint anti-PD-1 therapy, which makes CD1C a hot topic in cancer research.

References

• Sugita et al. 2000 Jul 18. doi: 10.1073/pnas.150236797
• Godfrey et al. 2018 Mar. doi: 10.1016/j.immuni.2018.03.009
• Wun et al. 2018 Apr. doi: 10.1038/s41590-018-0065-7
• Binnewies et al. 2019 Apr. doi: 10.1016/j.cell.2019.02.005
• D'Souza et al. 2019 Feb. doi: 10.1371/journal.ppat.1007567
• Mayassi et al. 2021 Jul. doi: 10.1038/s41586-021-03578-0