ABSTRACT
The human natural killer gene complex (NKC) encodes for numerous C-type lectin-like receptors (CTLR), which are expressed on various immune cells including natural killer (NK) cells and myeloid cells. Certain activation-induced, NKC-encoded CTLR are grouped into the C-type lectin domain family 2 (CLEC2 family) which, in humans, comprises AICL (CLEC2B), CD69 (CLEC2C), and LLT1 (CLEC2D). In this paper, we characterize a novel member of the CLEC2 family, the human orphan gene CLEC2A. The C-type lectin-like domain (CTLD) of CLEC2A is most similar to the CTLD of LLT1 ( approximately 60% similarity). Like mouse CLEC2 family members Clr-b and Clr-g, CLEC2A lacks two highly conserved cysteines (Cys4 and Cys5), which form an intramolecular bond in the CTLD of most CTLR. Alternative splicing of exon 2 and of two distinct terminal exons (exon 5A/B), respectively, gives rise to four CLEC2A variants differing in the usage of the transmembrane domain and/or in the carboxyterminal portion of the CTLD. CLEC2A transcripts were detected primarily in myeloid cell lines, but not in epithelial cell lines. In tissues, CLEC2A is selectively expressed in the skin and, at lower abundance, in hematopoietic and gonadal tissues. Finally, we show that the CLEC2A1 variant is readily expressed at the cell surface, where it may serve as a ligand for NKC-encoded NK receptors.
Subject(s)
Alternative Splicing , Antigens, CD/genetics , Antigens, Differentiation, T-Lymphocyte/genetics , Lectins, C-Type/genetics , Membrane Glycoproteins/genetics , Receptors, Cell Surface/genetics , Skin/metabolism , Amino Acid Sequence , Base Sequence , Cloning, Molecular , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Killer Cells, Natural , Lectins, C-Type/metabolism , Molecular Sequence Data , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Amino Acid , Skin/pathology , Transfection , U937 Cells/metabolismABSTRACT
The complete set of currently known streptococcal superantigens (SAgs) was tested for efficacy to induce in vitro cytokine responses from 5 different blood donors using the Luminex 100 system. Cytokine responses varied significantly between individual SAgs and between donors with a mixed Th1/Th2 response in 3 donors and a predominantly Th1 or Th2 response in the other 2 donors. Our results suggest that streptococcal SAgs might be involved not only in acute streptococcal diseases but also in chronic inflammation and autoimmune diseases.
Subject(s)
Cytokines/metabolism , Streptococcal Infections/immunology , Superantigens/immunology , Th1 Cells/metabolism , Th2 Cells/metabolism , Cells, Cultured , Cytokines/biosynthesis , Cytokines/immunology , Humans , Recombinant Proteins , Streptococcal Infections/metabolism , Streptococcal Infections/microbiology , Streptococcus/immunology , Superantigens/metabolism , Th1 Cells/drug effects , Th1 Cells/immunology , Th2 Cells/drug effects , Th2 Cells/immunologyABSTRACT
Eight different batches of intravenous immunoglobulin from 3 different manufacturers were tested for neutralizing activities against all currently known streptococcal superantigens. Statistically significant variation among different intravenous immunoglobulin preparations (P<.0001) and between individual streptococcal superantigens (P<.0001) was observed. These results might be helpful for optimizing the type and dose of intravenous immunoglobulin used in adjunctive therapy for severe invasive streptococcal disease.
