Quantitative analysis of the T cell receptor signaling network in response to altered peptide ligands

Understanding the adaptive immune system poses a great conceptual challenge. It has evolved to respond to foreign invaders with exquisite sensitivity and selectivity. In particular, the T cell branch of the immune system is trained to distinguish between self and non-self. This requires that a single receptor, the T cell receptor, bind to multiple ligands resulting in different cell fates, based in part on the avidity of the ligand. To address the question of ligand affinity discrimination in T cells, several T cell lines, both mouse and human, were screened for their ability to exhibit multiple cell fates in response to stimulation through the T cell receptor. A hybridoma system was identified that exhibits different levels of both apoptosis and cytokine production in response to three altered peptide ligands. We investigated how the consequent downstream signaling networks integrate to ultimately govern avidity-appropriate T cell responses in this hybridoma system. Here, we hypothesized that a quantitative combination of key downstream network signals can effectively represent the information processing generated by TCR ligation, providing a model capable of interpreting and predicting T cell functional responses.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Wille, Lucia

Advisor dc:contributor.advisor

• Douglas A. Lauffenburger.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/34576

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34576