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The Ly-49 family of natural killer cell receptors Brennan, John A.
Abstract
This thesis investigates the nature of receptors involved in target cell recognition by natural killer (NK) cells. N K cells are thought to scan for self class I major histocompatibility complex (MHC) antigens, receive negative signals from interactions with these molecules, and lyse those cells which are unable to deliver protective signals. This system ensures that cells which have extinguished expression of class I M H C and evade T cell immunity are detected by N K cells. Ly- 49A was the first N K cell receptor found to receive inhibitory signals from class I MHC on opposing cells. Because Ly-49A is expressed by a subset of N K cells and recognizes only a fraction of class I molecules, additional subsets of N K cells are thought to exist which express receptors for class I molecules not recognized by Ly- 49A. Ly-49A is a type II transmembrane protein belonging to a group of related molecules encoded by a murine multigene family. The expression patterns and functional activities of other members of the Ly-49 gene family was the topic of this thesis. Ly-49A and Ly-49C expression was shown to identify distinct single positive, double positive, and double negative subsets of N K cells. Both Ly-49A and Ly-49C were found to mediate adhesion to class I MHC on a variety of cell lines. The specificity of these receptors was shown to be distinct but overlapping, with Ly-49C having a much broader range of class I ligands. All members of the Ly-49 family have an extracellular region homologous to the carbohydrate recognition domain of C-type lectins. The functional relevance of this domain was demonstrated by the inhibition of Ly-49C-mediated cell adhesion by both exogenous polysaccharides as well as by the modification of target cell surface carbohydrates. This suggests that the glycosylation of class I MHC may be a critical element in Ly-49 recognition. These combined results support the hypothesis that Ly-49 is a family of N K cell receptors with related, but distinct functions. Ly-49A and Ly-49C are both expressed by NK cells, but not by the same NK cells, and they both bind to class I MHC molecules, but not the same class I molecules. These receptors may therefore be responsible for the generation of an NK cell repertoire capable of recognizing cells which lose expression of single class I molecules.
Item Metadata
Title |
The Ly-49 family of natural killer cell receptors
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
1996
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Description |
This thesis investigates the nature of receptors involved in target cell
recognition by natural killer (NK) cells. N K cells are thought to scan for self class I
major histocompatibility complex (MHC) antigens, receive negative signals from
interactions with these molecules, and lyse those cells which are unable to deliver
protective signals. This system ensures that cells which have extinguished
expression of class I M H C and evade T cell immunity are detected by N K cells. Ly-
49A was the first N K cell receptor found to receive inhibitory signals from class I
MHC on opposing cells. Because Ly-49A is expressed by a subset of N K cells and
recognizes only a fraction of class I molecules, additional subsets of N K cells are
thought to exist which express receptors for class I molecules not recognized by Ly-
49A.
Ly-49A is a type II transmembrane protein belonging to a group of related
molecules encoded by a murine multigene family. The expression patterns and
functional activities of other members of the Ly-49 gene family was the topic of this
thesis. Ly-49A and Ly-49C expression was shown to identify distinct single
positive, double positive, and double negative subsets of N K cells. Both Ly-49A
and Ly-49C were found to mediate adhesion to class I MHC on a variety of cell
lines. The specificity of these receptors was shown to be distinct but overlapping,
with Ly-49C having a much broader range of class I ligands. All members of the
Ly-49 family have an extracellular region homologous to the carbohydrate
recognition domain of C-type lectins. The functional relevance of this domain was
demonstrated by the inhibition of Ly-49C-mediated cell adhesion by both
exogenous polysaccharides as well as by the modification of target cell surface
carbohydrates. This suggests that the glycosylation of class I MHC may be a
critical element in Ly-49 recognition.
These combined results support the hypothesis that Ly-49 is a family of N K
cell receptors with related, but distinct functions. Ly-49A and Ly-49C are both expressed by NK cells, but not by the same NK cells, and they both bind to class I
MHC molecules, but not the same class I molecules. These receptors may therefore
be responsible for the generation of an NK cell repertoire capable of recognizing
cells which lose expression of single class I molecules.
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Extent |
9279328 bytes
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Genre | |
Type | |
File Format |
application/pdf
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Language |
eng
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Date Available |
2009-03-20
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0087916
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
1996-05
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Item Media
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.