Limits...
Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells.

Exley M, Garcia J, Balk SP, Porcelli S - J. Exp. Med. (1997)

Bottom Line: However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Invariant Vα24+ T  cells responded to chimeric CD1d  with intracellular CD1a. (a) FACS®  profiles of C1R CD1d (left) and  CD1d/a chimera (right) transfectants stained with normal mouse  serum (open histogram) or 42.1  CD1d-specific mAb (solid histogram). (b) DN2.D6 T cell clone  (105/well) was incubated with  unfixed C1R human B cell  CD1d/a chimera or mock transfectants (105/well) and IFN-γ  cytokine ELISA results obtained.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2198960&req=5

Figure 7: Invariant Vα24+ T cells responded to chimeric CD1d with intracellular CD1a. (a) FACS® profiles of C1R CD1d (left) and CD1d/a chimera (right) transfectants stained with normal mouse serum (open histogram) or 42.1 CD1d-specific mAb (solid histogram). (b) DN2.D6 T cell clone (105/well) was incubated with unfixed C1R human B cell CD1d/a chimera or mock transfectants (105/well) and IFN-γ cytokine ELISA results obtained.

Mentions: Human CD1b, c, d, and murine CD1d, but not human CD1a, have short cytoplasmic tails containing a sequence motif, Tyr-X-X-Z (where X is any amino acid and Z is a hydrophobic amino acid), shown to regulate the intracellular trafficking of many transmembrane proteins (54). Previous studies demonstrated a critical role for this motif in the endosomal localization of human CD1b (36). To determine whether this sequence is necessary for the cell surface expression and function of CD1d, the transmembrane domain and cytoplasmic tail from CD1a was fused to the CD1d ectodomain. A C1R cell line transfected with this CD1d-CD1a chimera expressed moderate levels of CD1d at the cell surface (Fig. 7 a). The level of CD1d expression was lower than in the C1R line expressing wild-type CD1d, as this latter line was initially sorted for CD1d+ cells.


Requirements for CD1d recognition by human invariant Valpha24+ CD4-CD8- T cells.

Exley M, Garcia J, Balk SP, Porcelli S - J. Exp. Med. (1997)

Invariant Vα24+ T  cells responded to chimeric CD1d  with intracellular CD1a. (a) FACS®  profiles of C1R CD1d (left) and  CD1d/a chimera (right) transfectants stained with normal mouse  serum (open histogram) or 42.1  CD1d-specific mAb (solid histogram). (b) DN2.D6 T cell clone  (105/well) was incubated with  unfixed C1R human B cell  CD1d/a chimera or mock transfectants (105/well) and IFN-γ  cytokine ELISA results obtained.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2198960&req=5

Figure 7: Invariant Vα24+ T cells responded to chimeric CD1d with intracellular CD1a. (a) FACS® profiles of C1R CD1d (left) and CD1d/a chimera (right) transfectants stained with normal mouse serum (open histogram) or 42.1 CD1d-specific mAb (solid histogram). (b) DN2.D6 T cell clone (105/well) was incubated with unfixed C1R human B cell CD1d/a chimera or mock transfectants (105/well) and IFN-γ cytokine ELISA results obtained.
Mentions: Human CD1b, c, d, and murine CD1d, but not human CD1a, have short cytoplasmic tails containing a sequence motif, Tyr-X-X-Z (where X is any amino acid and Z is a hydrophobic amino acid), shown to regulate the intracellular trafficking of many transmembrane proteins (54). Previous studies demonstrated a critical role for this motif in the endosomal localization of human CD1b (36). To determine whether this sequence is necessary for the cell surface expression and function of CD1d, the transmembrane domain and cytoplasmic tail from CD1a was fused to the CD1d ectodomain. A C1R cell line transfected with this CD1d-CD1a chimera expressed moderate levels of CD1d at the cell surface (Fig. 7 a). The level of CD1d expression was lower than in the C1R line expressing wild-type CD1d, as this latter line was initially sorted for CD1d+ cells.

Bottom Line: However, in contrast to NK cells, they did not express killer inhibitory receptors, CD16, CD56, or CD57.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.

View Article: PubMed Central - PubMed

Affiliation: Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus