The functional characterization ofgp180, a novel CD8 ligand expressed by intestinal epithelial cells.
Item
-
Title
-
The functional characterization ofgp180, a novel CD8 ligand expressed by intestinal epithelial cells.
-
Identifier
-
AAI9908297
-
identifier
-
9908297
-
Creator
-
Campbell, Nicola Anne.
-
Contributor
-
Adviser: Lloyd Mayer
-
Date
-
1998
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Health Sciences, Immunology | Biology, Cell | Biology, Molecular
-
Abstract
-
Studies performed have shown that intestinal epithetical cells (IECs) express a 180 kd glycoprotein, gp180, which binds to CD8, activates CD8-associated p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} and appears to be important in suppressor T cell activation by normal IECs. In contrast to intact IECs, purified gp180 is unable to induce T cell proliferation and does not activate the TCR-associated p59{dollar}\rm\sp{lcub}fyn{rcub}{dollar} kinase. Class lb molecules expressed on IECs, such as CD1d, have recently been shown to play a role in antigen presentation to T cells. Anti-CD1d monoclonal antibodies inhibit the proliferation of CD8{dollar}\sp+{dollar} T cells induced by IECs although CD1d itself does not bind to CD8. Immunoprecipitation and ELISA studies indicate that gp180 and CD1d associate on the surface of IECs such that this complex may interact with the CD8:TCR complex on the surface of CD8{dollar}\sp+{dollar} suppressor T cells.;To further establish the validity of this model, a CD1d cDNA transfectant (FO-1 D5) or an untransfected control, FO-1, was used in T cell co-cultures. Only FO-1 D5 was able to activate p59{dollar}\rm\sp{lcub}fyn{rcub}{dollar} but ot p56{dollar}\rm\sp{lcub}lck{rcub}{dollar}. To confirm these findings, freshly isolated IECs were cultured with PBTs in the presence or absence of an anti-CD1d mAb, D5 or an anti-gp180 mAb, B9. Activation of p59{dollar}\rm\sp{lcub}fyn{rcub}{dollar} but not p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} was locked by D5 while mAb B9 inhibited IEC-induced activation of p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} but not p59{dollar}\rm\sp{lcub}fyn{rcub}.{dollar} In addition, it appeared that IEC-stimulated CD8{dollar}\sp+{dollar} T cells signal via a PKC-independent pathway. This is in contrast to class I restricted CTL which use both the PKC-dependent and independent pathways. Thus, the C01d:gp180 complex on the surface of IECs may act as a novel ligand for the TCR:CD8 complex on suppressor T cells. Phosphorylation of p59{dollar}\rm\sp{lcub}fyn{rcub}{dollar} and p56{dollar}\rm\sp{lcub}lck{rcub}{dollar} results in the recruitment of downstream kinases and substrates resulting in the complete activation of CD8{dollar}\sp+{dollar} suppressor T cells.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
