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

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.

CD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses

“…Our data further support a CD1d-CD36 axis by which CD1d could in turn modulate the internalization of CD36 and consequently control lipid uptake. It is worth noting that a similar function could be also relevant to other CD1 family members expressed in human cells, such as CD1b or CD1c, as tetramers from these molecules have also been shown to bind CD36 in human monocytes 28 . CD1d molecules have a short intracellular tail which has been shown to control their intracellular trafficking and rate of internalization in steady state 38,39 .…”

“…In line with this, other surface molecules -such as CD146-have been shown to modulate CD36 internalization during lipid uptake ultimately controlling macrophage activation 35 . Interestingly, a recent technical report has identified CD36 as a ligand for human CD1 tetramers 28 . While the physiological relevance of this observation remains unexplored, the authors suggest that CD36 could play a role in the pathways of lipid loading into CD1 molecules.…”

“…The uptake of modified lipoproteins by macrophages is largely mediated by the scavenger receptor CD36 which plays a key role in the regulation of lipid transport and cellular metabolism [25][26][27] . Interestingly, a recent technical report proposed the lipid transporter CD36 as a ligand for CD1 molecules demonstrating the binding of CD1 tetramers to CD36 in human monocytes, with possible implications for the functions of these proteins 28 . This prompted us to investigate whether CD36 could contribute to the increase in lipid uptake in CD1d-KO cells.…”

Rational design of a hydrolysis-resistant mycobacterial phosphoglycolipid antigen presented by CD1c to T cells

“…Human T-cell lines were stained with tetramers at 2 μg/ml in PBS containing 1% BSA and 0.01% sodium azide. Cells were preincubated with unlabeled CD36 antibody (5-271; Biolegend) for 10 min at RT ( 37 ). Tetramer was added and incubated for 10 min at RT in the dark, followed by addition of cell surface antibodies for 10 min at RT.…”

Data_Sheet_1.docx

“…Immunofluorescence assays of tissue sections showed that BTK was mainly located in macrophages at the junction of cancer nest and stroma, and negatively correlated with the abundance of NK cells (Supplementary Figures 9C,D), suggesting that BTK promotes tumor progression by promoting local immunosuppression. As a specific marker of dendritic cells, Cd1c has the function of regulating antigen presentation of dendritic cells and improving TME (Yuan et al, 2019;Gherardin et al, 2021). We found that both mRNA and protein expression of Cd1c were down-regulated in LUAD tumor tissues (Supplementary Figures 4, 5), while the down-regulation of Cd1c was associated with poor survival (Supplementary Figure 4).…”