Requirements for CD 1 d Recognition by Human Invariant V a 24 1 CD 4 2 CD 8 2 T Cells

A subset of human CD4 2 CD8 2 T cells that expresses an invariant V a 24-J a Q T cell receptor (TCR)a chain, paired predominantly with V b 11, has been identified. A series of these V a 24 V b 11 clones were shown to have TCRb 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 V a 24 1 clones recognized the MHC class I–like CD16 molecule and discriminated between CD1d and other closely related human CD1 proteins, indicating that recognition was TCRmediated. 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 a 24 1 CD4 2 CD8 2 T cells, and presumably the homologous murine NK1 1 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.