Asymmetric T cell division and the self-renewal of specific immunity / Maria L. Ciocca.

Ciocca, Maria L.
viii, 97 p. : ill. (some col.) ; 29 cm.
Local subjects:
Penn dissertations -- Cell and molecular biology.
Cell and molecular biology -- Penn dissertations.
During clonal selection of a T cell in response to infection of a host with an invasive pathogen, the host must respond by producing at least two required and disparate cell populations—one that is responsible for controlling the current infection and another that is required to retain the T cell clone for protection against future insults. This diversity within the T cell response may be generated through the use of asymmetric cell division. How T cells may use asymmetric division and to what extent this molecular process plays a role in adaptive immunity is not well understood. Here we suggest that asymmetric division during the initial T cell response segregates proteins by a unique mechanism that involves unequal degradation of a fate-determinate secondary to polarized segregation of the protein degradation machinery. Furthermore, we provide data to extend the principle of asymmetric division to the memory cell response, suggesting that certain antigen-experienced lymphocytes can re-iteratively undergo this process to generate diversity when once again faced with a pathogenic challenge. Together, these results suggest highly conserved principles of stem-cell biology may be regulating the generation of diversity in the adaptive immune response both during primary and recurrent infection.
Adviser: Steven L. Reiner.
Thesis (Ph.D. in Cell and Molecular Biology) -- University of Pennsylvania, 2012.
Includes bibliographical references.
Reiner, Steven L., advisor.
Speck, Nancy A. committee member.
Koretzky, Gary A. committee member.
Orange, Jordan S. committee member.
Pear, Warren S. committee member.
University of Pennsylvania. Cell and Molecular Biology.
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