Date of Award

2026-05-01

Degree Name

Master of Science

Department

Biological Sciences

Advisor(s)

Charlotte M. Vines

Abstract

Activation of T lymphocytes is the main event that occurs in the adaptive immune response after engagement of the T cell receptor (TCR) with the peptide of the major histocompatibility complex (pMHC) molecules that are demonstrated by antigen presenting cells [1]. A key step in this process is the recruitment and activation of the zeta chain associated protein of 70 kDa (ZAP-70). ZAP-70 couples TCR engagement to downstream intracellular signaling pathways through phosphorylation of tyrosine residues within intracellular tyrosine activation motifs (ITAMs) [2]. Although there have been extensive studies on the signaling response through TCR activation, the regulatory influence of chemokine receptor co-stimulation, particularly C-C chemokine receptor 7 (CCR7), on ZAP-70 activation remains unclear. This study investigates the mechanisms coordinating ZAP-70 recruitment and activation during early TCR-mediated signaling with CCR7 co-stimulation. Using a combination of biochemical assays and phosphorylation analysis, this study examines how CCR7 activation affects TCR signaling, including ZAP-70 localization to the TCR, phosphorylation kinetics, and downstream signaling pathways. Previous studies have shown that CCR7 co-stimulation leads to prolonged and enhanced ZAP-70 activation [3]. However, the specific functional domains of ZAP-70 involved in coordinating downstream signaling through CCR7 have not been fully characterized. We hypothesize that CCR7 co-stimulation enhances activation of ZAP-70 and promotes sustained phosphorylation of downstream signaling mediators through calcium mobilization, migration, and adhesion. This will demonstrate that CCR7 is an important modulator of intracellular signaling during antigen recognition. These findings may support the development of therapeutic strategies targeting T cell activation in autoimmune disease, chronic inflammation, and immunotherapy applications.

Language

en

Provenance

Received from ProQuest

File Size

47 p.

File Format

application/pdf

Rights Holder

Vivian Torres

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