CD1a

CD1a is an MHC-class-I-like antigen-presenting molecule that binds lipid antigens and activates CD1-restricted T cells^[1]. Mechanistically, CD1 proteins bind hydrophobic lipid chains in antigen-binding grooves and position polar headgroups for TCR recognition^[2]. In human skin, Langerhans cells express very high levels of CD1a, making CD1a lipid antigen presentation a central pathway for studying skin-resident T-cell activation^[3]. CD1a-reactive T cells form a normal human skin T-cell population, and CD1a tetramers without added antigen stained approximately 1% of skin T cells in every tested subject^[4]. In disease models, human CD1a transgenic mice showed stronger systemic inflammation after imiquimod- or MC903-induced skin inflammation, and CD1a-blocking antibodies reduced CD1a-dependent inflammatory responses^[5]. Compared with related isoforms, CD1a belongs to group 1 CD1 molecules with CD1b and CD1c, whereas CD1d belongs to group 2 and presents lipids to iNKT cells^[6]. CD1b and CD1c survey distinct intracellular compartments, supporting isoform-specific lipid antigen sampling rather than redundant CD1 function^[7]. For experimental applications, CD1a tetramers enable tracking of CD1a-specific T cells, while inhibitory natural skin lipids and CD1a-blocking antibodies provide tools to test CD1a-dependent inflammation^[4][5][8].