CD1c-mediated T-cell recognition of isoprenoid glycolipids in Mycobacterium tuberculosis infection

The discovery of the CD1 antigen presentation pathway has expanded the spec trum of T-cell antigens to include lipids(1-4), but the range of natural li pid antigens and functions of CD1-restricted T cells in vivo remain poorly understood. Here we show that the T-cell antigen receptor and the CD1c prot ein mediate recognition of an evolutionarily conserved family of isoprenoid glycolipids whose members include essential components of protein glycosyl ation and cell-wall synthesis pathways. A CD1c-restricted, mycobacteria-spe cific T-cell line recognized two previously unknown mycobacterial hexosyl-1 -phosphoisoprenoids and structurally related mannosyl-beta 1-phosphodolicho ls. Responses to mannosyl-b1-phosphodolichols were common among CD1c-restri cted T-cell lines and peripheral blood T lymphocytes of human subjects rece ntly infected with M. tuberculosis, but were not seen in naive control subj ects. These results define a new class of broadly distributed lipid antigen s presented by the CD1 system during infection in vivo and suggest an immun e mechanism for recognition of senescent or transformed cells that are know n to have altered dolichol lipids.