MAJOR histocompatibility complex (MHC) class I and class II molecules bind immunogenic peptides and present them to lymphocytes bearing the alpha beta T-cell antigen receptor (TCR)(1-4). An analogous antigen-presenting function also has been proposed for the non-MHC-encoded CDI molecules : a family of non-polymorphic, beta(2)-microglobulin-associated glycoproteins(5-8) expressed on most professional antigen-presenting cells(9-11). In support of this hypothesis, CD1 molecules are recognized by selected CD4(-)CD8(-)alpha beta or gamma delta TCR(+) T-cell clones(12-14), and we have recently shown that CD1 molecules restrict the recognition of foreign microbial antigens by alpha beta TCR(+) T cells(10). But the substantial structural divergence of CD1 from MHC class I and class II molecules(7), raises the possibility that the antigens presented by the CD1 system may differ fundamentally from those presented by MHC-encoded molecules. Here we report that a purified CD1b-restricted antigen of Mycobacterium tuberculosis presented to alpha beta TCR(+) T cells is mycolic acid, a family of alpha-branched, beta-hydroxy, long-chain fatty acids found in mycobacteria(15-16). This example of non-protein microbial antigen recognition suggests that alpha beta TCR(+) T cells recognize a broader range of antigens than previously appreciated and that at least one member of the CD1 family has evolved the ability to present lipid antigens.