Research ResourceT CELLS

CD36 family members are TCR-independent ligands for CD1 antigen–presenting molecules

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Science Immunology  25 Jun 2021:
Vol. 6, Issue 60, eabg4176
DOI: 10.1126/sciimmunol.abg4176

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CD36 blockade provides CD1 clarity

A subset of T cells detects lipids presented by CD1c. However, studying CD1c-restricted T cells has been limited because CD1c tetramers also bind to various blood cells. Here, Gherardin et al. determined that CD1c tetramers bound to CD36 family members, with CD36 being widely expressed on various different blood cells. Blocking CD36 with an antibody enabled the precise detection of CD1c-restricted T cells, facilitating a deep analysis of their phenotype and TCR repertoire. To a lesser extent, both CD1b and CD1d also interacted with CD36 family members, and CD36 blockade improved the specificity of CD1b and CD1d tetramers. This resource presents a protocol by which CD1c-restricted T cells can be clearly stained and isolated, opening the door for a more precise study of these T cells.


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.

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