Characterization of a 180 kDa intestinal epithelial cell membrane glycoprotein,gp180: A candidate molecule mediating T cell:epithelial cell interactions.
Item
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Title
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Characterization of a 180 kDa intestinal epithelial cell membrane glycoprotein,gp180: A candidate molecule mediating T cell:epithelial cell interactions.
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Identifier
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AAI9720155
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identifier
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9720155
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Creator
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Yio, Xian Yang.
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Contributor
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Adviser: Lloyd Mayer
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Immunology | Biology, Molecular | Biology, Cell
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Abstract
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Normal intestinal epithelial cells (IECs) have been recognized as a potential immuno-regulatory cell in the mucosa, capable of presenting antigens in a non-class I/class II MHC restricted manner and promoting the proliferation of CD8{dollar}\sp+{dollar} suppressor T cells which may play an important role in oral tolerance and immune hyporesponsiveness in the gut. In this thesis, the molecules involved in T cell:IEC interactions were studied. The results demonstrated that, the induction of CD8{dollar}\sp+{dollar} suppressor T cell activation by IECs appears to be linked to the binding of CD8 molecules on the T cell surface and activation of its associated kinase, p56{dollar}\rm\sp{lcub}lck{rcub}{dollar}. Co-culture of 3G8, a human CD8 transfectants, with IECs but not with monocytes activated p56{dollar}\rm\sp{lcub}lck{rcub}{dollar}, whereas p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} was preferentially activated in 3G4 cells, a human CD4 transfectants, by monocytes. Pretreatment of IECs with anti-IEC mAbs, B9 and L12, inhibited CD8 associated p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} activation and T cell proliferation. These mAbs recognize a 180 kDa IECs membrane glycoprotein (gp180) which is heavily N-glycosylated. Functionally, gp180 has been shown capable of binding to PBT cells and activate CD8 associated p56{dollar}\rm\sp{lcub}lck{rcub}{dollar}. The sequence analysis of peptide fragments from gp180 demonstrated high homology to the N-terminal regions of carcinoembryonic antigen (CEA), and modest homology to adhesion molecules and IgG. It appears that gp180 is a novel member of the CEA family which can mediate interactions with CD8 on T cells.;In patients with inflammatory bowel disease (IBD), IECs failed to activate CD8{dollar}\sp+{dollar} T cells, and gp180 expression on IECs was abnormally distributed or reduced to absent, as shown by both Immunohistochemical and flow cytometric analysis. The abnormal expression of gp180 in IBD correlated with the inability of the IEC to activate CD8 associated p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} in T cells.;Taken together, the CD8 molecule on T cells and gp180, a novel CEA subfamily member, on IECs appear to be necessary, but not sufficient, for IEC induction of CD8{dollar}\sp+{dollar} T cell activation. Activation of p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} is involved in coupling such interactions to the downstream signaling components.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
