REQUIREMENTS FOR CD1D RECOGNITION BY HUMAN INVARIANT V-ALPHA-24(-)CD8(-) T-CELLS() CD4()

A subset of human CD4(-)CD8(-) T cells that expresses an invariant V a lpha 24-J alpha Q T cell receptor (TCR)-alpha chain, paired predominan tly 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 expres s the natural killer (NK) locus-encoded C-type lectins NKR-P1A, CD94, and CD69. However, in contrast to NK cells, they did not express kille r inhibitory receptors, CD16, CD56, or CD57. All invariant Va24(+) clo nes recognized the MHC class I-like CD16 molecule and discriminated be tween CD1d and other closely related human CD1 proteins, indicating th at recognition was TCR-mediated. Recognition was not dependent upon an endosomal targeting motif in the cytoplasmic tail of CD1d. Upon activ ation by anti-CD3 or CD1d, the clones produced both Th1 and Th2 cytoki nes. These results demonstrate that human invariant V alpha 24(+) CD4( -)CD8(-) T cells, and presumably the homologous murine NK1(+) T cell p opulation, 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.