Synthetic phenyl pentamethyldihydrobenzofuran sulfonates (PPBF) were identified as CD1d-presented antigens for a fortuitously generated human T cell clone from a random blood bank donor, ABd (Van Rhijn et al. 2004). Despite the isolation of many clones that share PPBF- and CD1d-specificity and similar TCR a-chains (Almeida et al. 2021), there are currently no insights in possible natural targets of these cells or their relevance for human health. Later, T cells with ABd-like TCR a-chains and antigen specificity were found to be highly enriched in Crohn’s disease patients, but not in ulcerative colitis controls or healthy controls and were re-named “Crohn’s disease-Associated Invariant T” (CAIT) cells (Rosati et al. 2022; Minervina et al. 2022). Because humans are not exposed to PPBF, we want to know whether natural compounds can stimulate CAIT cells and whether live CAIT cells can be isolated from the affected tissues of Crohn’s disease patients. Using tissue taken from small intestine biopsies we isolated a long term TRAV12-1+ T cell line that was activated by CD1d and PPBF. Further, hydrophobic extracts from stool or human ileal washings activated the original ABd reporter CAIT cell line in a CD1d-dependent manner. These results demonstrate the presence of live, antigen-responsive CAIT cells at or near the site of disease and suggest the presence of natural antigens in human stool.