Requirements for CD1d recognition by human invariant Vα24⁺ CD4^- CD8^- T cells

A subset of human CD4^- CD8^- T cells that expresses an invariant Vα24- JαQ T cell receptor (TCR)-α chain, paired predominantly with Vβ11, has been identified. A series of these Vα24 Vβ11 clones were shown to have TCR- β CDR3 diversity and express the natural killer (NK) locus-encoded C-type lectins NKR P1A, CD94, and CD69. However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57. All invariant Vα24⁺ clones recognized the MHC class I-like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCR-mediated. Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. Upon activation by anti CD3 or CD1d, the clones produced both Th1 and Th2 cytokines. These results demonstrate that human invariant Vα24⁺ CD4^- CD8^- T cells, and presumably the homologous murine NK1⁺ T cell population, are CD1d reactive and functionally distinct from NK cells. The conservation of this cell population and of the CD1d ligand across species indicates an important immunological function.