Requirements for CD1d recognition by human invariant V alpha 24(+) CD4(-)CD8(-) T cells

A subset of human CD4(-)CD8(-) T cells that expresses an invariant V alpha 24-J alpha Q T cell receptor (TCR)-alpha chain, paired predominantly with V beta 11, has been identified. A series of these V alpha 24 V beta 11 clones were shown to have TCR-beta 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 Va24(+) 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 V alpha 24(+) 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.