Shifting Paradigms: T Cells, FlipFlops, and Reversed T Cells

Antibuddies

You must have come across the fundamental concepts of T cell development during your immunology class. Briefly, in the thymus, T cells expressing both CD4 and CD8 coreceptors interact with MHC molecules on thymic epithelial cells to make lineage fate decisions. CD4+ cells interact with MHCII and are called T helper cells while CD8+ cells interact with MHCI and are called cytotoxic T cells. Debates over the nitty-gritty of how this selection takes place have consisted of two main theories: “Strength of Signal model” and “Kinetic Signaling model”.

The “Strength of Signal model”, as the name suggests, focuses on the strength of the signal originating from T cell receptor (TCR) – coreceptor interactions with MHC molecules. A strong CD4-TCR signal gives rise to helper lineage while a weak CD8-TCR signal gives rise to cytotoxic lineage. According to the “Kinetic Signaling model”, the lineage decisions arise from the duration of the…

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