CD36 family members are TCR-independent ligands for CD1 antigen–presenting molecules
Nicholas A. Gherardin, Samuel J. Redmond, Hamish E. G. McWilliam, Catarina F. Almeida, Katherine H. A. Gourley, Rebecca Seneviratna, Shihan Li, Robert De Rose, Fiona Ross, Catriona V. Nguyen-Robertson, Shian Su, Matthew E. Ritchie, Jóse A. Villadangos, D. Branch Moody, Daniel G. Pellicci, Adam P. Uldrich, Dale I. Godfrey
Abstract
CD1c presents lipid-based antigens to CD1c-restricted T cells, which are thought to be a major component of the human T cell pool. However, the study of CD1c-restricted T cells is hampered by the presence of an abundantly expressed, non-T cell receptor (TCR) ligand for CD1c on blood cells, confounding analysis of TCR-mediated CD1c tetramer staining. Here, we identified the CD36 family (CD36, SR-B1, and LIMP-2) as ligands for CD1c, CD1b, and CD1d proteins and showed that CD36 is the receptor responsible for non-TCR-mediated CD1c tetramer staining of blood cells. Moreover, CD36 blockade clarified tetramer-based identification of CD1c-restricted T cells and improved identification of CD1b- and CD1d-restricted T cells. We used this technique to characterize CD1c-restricted T cells ex vivo and showed diverse phenotypic features, TCR repertoire, and antigen-specific subsets. Accordingly, this work will enable further studies into the biology of CD1 and human CD1-restricted T cells.