Question

1. What is allelic exclusion? And what are the three mechanisms mediating allelic exclusion.

2. If the beta chain successfully (productively) rearranged, produced a functional pre T cell receptor and the alpha chain now begins to rearrange, can the cell still differentiate into a gamma/delta T cell? If yes or no, why?

Answer 1

Allelic exclusion is a process by which only one allele of a gene is expressed while the other allele is silenced. For autosomal genes, diploid organisms inherit one copy from each parent. At least two distinct selection events can lead to allelic exclusion. The current genetic models to explain the establishment of Ig allelic exclusion fall into three categories: asynchronous recombination models, the stochastic model, and feedback inhibition models. Gamma delta T cells (γδ T cells) are T cells that have a distinctive T-cell receptor (TCR) on their surface. Most T cells are αβ (alpha beta) T cells with TCR composed of two glycoprotein chains called α (alpha) and β (beta) TCR chains. In contrast, gamma delta (γδ) T cells have a TCR that is made up of one γ (gamma) chain and one δ (delta) chain. This group of T cells is usually less common than αβ T cells, but are at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs).[1]

The antigenic molecules that activate gamma delta T cells are still largely unknown. However, γδ T cells are peculiar in that they do not seem to require antigen processing and major-histocompatibility-complex (MHC) presentation of peptide epitopes, although some recognize MHC class Ib molecules. Furthermore, γδ T cells are believed to have a prominent role in recognition of lipid antigens. They are of an invariant nature and may be triggered by alarm signals, such as heat shock proteins (HSP).