Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells.
A subset of human CD4-CD8- T cells that expresses an invariant Valpha24-JalphaQ T cell receptor (TCR)-alpha chain, paired predominantly with Vbeta11, has been identified. A series of these Valpha24 Vbeta11 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 Valpha24(+) 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 Valpha24+ 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.
Exley
M
M
Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
Garcia
J
J
Balk
S P
SP
Porcelli
S
S
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D015703:Antigens, CD; D016207:Cytokines; D016693:Receptors, Antigen, T-Cell, alpha-beta