Year of Award

2026

Document Type

Dissertation

Degree Type

Doctor of Philosophy (PhD)

Degree Name

Toxicology

Department or School/College

Division of Biological and Biomedical Sciences

Committee Chair

Scott Wetzel

Commitee Members

Zeina Jaffar, Kevan Roberts, Jesse Hay, Stephen Lodmell

Keywords

Adaptive immunity, T cell receptor (TCR), T cells, TCR Affinity, Trogocytosis, Trogocytosis-mediated signaling

Abstract

Trogocytosis is the contact-dependent transfer of plasma membrane and its associated proteins between cells. Unlike other forms of intercellular exchange, the transferred proteins often remain functional and are re-displayed on the trogocytosis-positive (trog+) recipient, allowing a cell to bear molecules it did not produce. CD4+ T cells acquire surface proteins this way while engaging antigen-presenting cells (APCs), yet the consequences for the individual trog+ cell remain poorly defined. Upon antigen recognition from APC, T cell receptor (TCR) affinity determines the strength and character of the intracellular signal generated. Our lab has previously shown that engagement of these acquired ligands elicits a cell-intrinsic signal, termed trogocytosismediated signaling, that promotes trog+ cell survival after APC withdrawal and drives differentiation toward a T helper 2 (TH2) program. Despite this chain of relationships, the precise impact of TCR affinity on trogocytosis efficiency, and what that means for the downstream signaling and differentiation outcomes in trog+ cells, remains largely uncharacterized. This gap in knowledge formed the central motivation for the present dissertation.

It was demonstrated for the first time, that TCR affinity governs trogocytosis efficiency, acting as a threshold that dictates whether a CD4+ T cell becomes trog+ during synapse formation. Sustained over five to seven days, this moderate-amplitude signal extends differentiation beyond TH2 into a T follicular helper (TFH) program, yielding a TFH2 subset that co-expresses GATA-3 and Bcl-6 with CXCR5 and PD1.

Collectively, these findings establish TCR affinity as a determinant of trogocytosis efficiency. They also position trogocytosis-mediated signaling as an affinity dependent mechanism by which antigen recognition quality shapes the resulting helper T cell lineage. Because GATA3 drives the IL-4 and IL-13 that promote IgE class switching, an affinity-tuned trog+ TFH2 program may favor IgE production, suggesting that trogocytosis-mediated signaling could contribute to the type I hypersensitivity underlying allergic disease.

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© Copyright 2026 Deborah Ebere Agbakwuru