Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The murine T cell surface molecules Ly-6C and Thy-1 are genetically and structurally distinct, yet they share two interesting properties: both are attached to the plasma membrane through a glycophosphatidylinositol linkage, and some mAb reactive with these molecules can activate T cells. Although mAb for Ly-6C and Thy-1 appear to mimic the function of physiologic ligands, direct evidence for the existence of these putative ligands has not been presented. In this report, we describe CTL clones that use Ly-6C and Thy-1 as accessory molecules for activation of cytolysis and the production of IFN-gamma based on inhibition of these functions with mAb. These studies were facilitated by the derivation of a nonactivating hamster IgM mAb specific for Ly-6C. CTL clones that use Ly-6C and Thy-1 as accessory molecules include a subpopulation of the previously described CD8+ alloreactive CTL that are not inhibited by mAb reactive with CD8, a CD8+ TCR-alpha/beta+ T cell clone specific for HSV glycoprotein D, and a CD4-CD8- TCR-gamma/delta+ T cell clone specific for HSV glycoprotein I. The role of Ly-6C and Thy-1 in target cell recognition is to some degree tissue-specific with respect to the APC/target cell. A mAb specific for Ly-6C appears to inhibit activation by prevention of adhesion between the effector cells and the target cells. This is the most direct evidence to date of a functional ligand for Ly-6C.
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PMID:Accessory molecules involved in antigen-mediated cytolysis and lymphokine production by cytotoxic T lymphocyte subsets. I. Identification of functions for the T cell surface molecules Ly-6C and Thy-1. 810 17

The present study examined self-tolerance for T cell receptor (TCR) alpha beta intestinal intraepithelial lymphocytes (iIELs) using the 2C transgenic (Tg) mouse model specific for a peptide antigen (Ag) presented by the class I major histocompatibility complex H-2Ld. Although Tg+ T cells were largely deleted from the periphery of Ag+ mice, equivalent numbers of Tg iIELs were present in Ag+ compared to Ag- mice. Tg iIELs in Ag- mice contained CD8 alpha beta, CD8 alpha alpha, and CD4-CD8- subsets, whereas only CD8 alpha alpha and CD4-CD8- Tg iIEL subsets were detected in Ag+ mice. Analysis of surface markers revealed that Tg iIELs in Ag+ mice expressed decreased levels of Thy-1 and increased CD45R/B220 as compared to Ag- Tg iIELs. In response to activation with exogenous peptide or immobilized anti-TCR mAB, iIELs from Ag- mice proliferated at high levels and produced interleukin (IL)-2 and interferon (IFN)-gamma, while Tg+ iIELs from Ag+ mice proliferated at low levels and failed to produce detectable IL-2 or IFN-gamma. Activation of sorted iIEL subsets from Ag- mice revealed that CD8 alpha alpha and CD4-CD8- subsets produced low levels of IL-2 and IFN-gamma in response to activation with antigen-presenting cells and added peptide or immobilized anti-TCR mAb, while CD8 alpha beta + iIELs responded to endogenous levels of peptide. In response to APC and exogenous peptide, sorted iIEL subsets from Ag+ mice produced IL-2 and IFN-gamma, and proliferated at greatly reduced levels compared to corresponding subsets from Ag- mice. Analysis of cytokine mRNA levels revealed that activation in vitro induced IL-2 mRNA only in Ag-, but not Ag+ iIELs, whereas a high level of IL-4 mRNA induction was detected in Tg+ iIELs from Ag+ mice, and to a lesser degree, from Ag- mice. These data suggest that tolerance for Tg+ iIELs resulted in the deletion of CD8 alpha beta + subsets and the persistence of Tg+ iIEL subsets with decreased sensitivity to endogenous levels of self-peptide. A comparison of the cytokine profiles expressed by Tg+ iIEL subsets in Ag- and Ag+ mice suggested that tolerance induction had involved the functional deviation of cells from TC1 (T helper-1-like) to a less inflammatory TC2 (T helper-2-like) phenotype capable of mediating humoral immune responses in the mucosa.
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PMID:Immune deviation of 2C transgenic intraepithelial lymphocytes in antigen-bearing hosts. 876 Aug 3

Human hematopoietic stem cells (HSCs) and progenitors can be isolated by enriching for a rare cell population with a combination of monoclonal antibodies (MAbs). Such an isolation scheme involves multi-step procedures including ficoll-density fractionation and presort enrichment followed by cell sorting. Over the past decade, various cell-surface and metabolic markers have been identified and used to isolate human HSCs and progenitors as summarized in Table 1. Among them, CD34 has become the most critical cell-surface marker for positively selecting a rare cell population (1,2). Within the CD34(+) cell population, the differential expression of Thy-1, CD38, and AC133 have been used to fractionate HSCs and progenitors. In order to subfractionate CD34(+) cells by these markers, the cells can be further purified by flow cytometry. HSCs can be further enriched into a Thy-1(+) (3-7), CD38(-lo) (8-10), Thy-1+ CD38(-lo) (11), or AC133+ (12,13) fraction of CD34(+) cells. Table 1 Commercially Available Cell-Surface and Metabolic Markers for Isolation of Human HSC and Progenitor Cells Marker Expression/Remark Fluorochrome conjugate recommended Reference Positive marker CD34 Positive FITC, PE, APC, BIO 1,2,33 Thy-1 Positive PE, BIO 3,4 AC133 Positive PE 12,34 Negative/low marker CD38 Negative /low FITC, PE, APC 8,9 HLA-DR( a ) Negative to low FITC, PE 35,36 Mature lineage marker, Lin- CD2 T-cell lineage FITC, PE, BIO 3 CD3 T-cell lineage FITC, PE, APC, BIO 3 CD19 B-cell lineage FITC, PE, APC, BIO 3 CD16 NK-cell lineage FITC, PE, APC, BIO 3 CD14 Myeloid lineage FITC, PE 3 CD15 Myeloid lineage FITC, PE 3 Glycophorin A Erythroid lineage FITC, PE 3 2nd Step reagent Avidin/Streptavidin For BIO MAb FITC, PE, APC, TXRD, PharRed, Cy-chrome( d ) Metabolic marker( b ) Rhodamine 123( c ) Low Mitochondria-binding dye 37,38 Hoechst 33342( c ) Low DNA-binding dye 39,40 Pyronin Y Low RNA-binding dye 39,40 Propidium iodide Negative to low Dead-cell exclusion Abbreviations: FBM, fetal bone marrow; MPB, mobilized peripheral blood; ABM, adult bone marrow; HSC, hematopoietic stem cells; FITC, fluorescein; PE, phycoerythrin; APC, allophycocyanin; TXRD, Texas red; BIO, biotinylated. ( a ) FBM, MPB HSCs express HLA-DR (41,42). ( b ) To isolate quiescent HSC. ( c ) Substrates for p-glycoprotein, encoded by MDR-1. HSC possess high levels of p-glycoprotein efflux activity. ( d ) Recommended for single laser flow cytometry only, lineage marker positive and PI positive cells can be excluded simultaneously.
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PMID:Method for purification of human hematopoietic stem cells by flow cytometry. 2143


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