T lymphocyte recognition of human group 1 CD1 molecules: Implications for innate and acquired immunity

Recent evidence has established that non-MHC-encoded molecules of the CD1 family mediate MHC-independent pathways for antigen presentation and T cell activation. Human group 1 CD1 molecules (CD1a, CD1b, CD1c) are expressed mainly on professional antigen-presenting cells, and mediate presentation of microbial lipid and glycolipid antigens to T cells. These group 1 CD1 molecules differentially sample distinct endocytic compartments that may contain different sets of lipid antigens derived from intracellular microbes, and activate antigen-specific T cells. These T cells lyse infected antigen-presenting cells and secrete Th1 cytokines, such as interferon- γ, and granulysin, a potent antimicrobial protein, and thus can control microbial infection. Reactivity to CD1a, b, and c molecules in the absence of foreign antigen has also been detected in T cells bearing αβ and γδ TCRs. These T cells may recognize self-lipid antigens and are considered to be autoreactive. In particular, the main tissue subset of γδ T cells (V δ 1 + subset) show prominent reactivity to CD1c, and produce interferon- γ and granulysin. These CD1c directly reactive T cells may mediate immunity against microbial infection even before antigen-specific T cells differentiate and expand. Together, human CD1a, b and c molecules elicit T cell-dependent immunity to the universe of foreign and self-lipid antigens in both innate and acquired immunity settings.