Group 1 CD1 (CD1a, -b, and -c) presents self and foreign lipid antigens to multiple T-cell subsets in humans. However, in the absence of a suitable animal model, the specific functions and developmental requirements of these T cells remain unknown. To study group 1 CD1-restricted T cells in vivo, we generated double transgenic mice (HJ1Tg/hCD1Tg) that express group 1 CD1 molecules in a similar pattern to that observed in humans (hCD1Tg) as well as a TCR derived from a CD1b-autoreactive T-cell line (HJ1Tg). Using this model, we found that similar to CD1d-restricted NKT cells, HJ1 T cells exhibit an activated phenotype (CD44(hi)CD69(+)CD122(+)) and a subset of HJ1 T cells expresses NK1.1 and is selected by CD1b-expressing hematopoietic cells. HJ1 T cells secrete proinflammatory cytokines in response to stimulation with CD1b-expressing dendritic cells derived from humans as well as hCD1Tg mice, suggesting that they recognize species conserved self-lipid antigen(s). Importantly, this basal autoreactivity is enhanced by TLR-mediated signaling and HJ1 T cells can be activated and confer protection against Listeria infection. Taken together, our data indicate that CD1b-autoreactive T cells, unlike mycobacterial lipid antigen-specific T cells, are innate-like T cells that may contribute to early anti-microbial host defense