In T cells, allelic exclusion of the ?-chain locus is relatively ineffective, resulting in the production of some T cells with two T-cell receptors of differing antigen specificity on their cell surface

Question

A. Will both these receptors have to pass positive selection for the cell to survive? Explain your answer.
B. Will both receptors have to pass negative selection for the cell to survive? Explain your answer.
C. Is there a potential problem in having T cells with dual specificity surviving these selection processes and being exported to the periphery?

What will be an ideal response?

Answer 1

A. Only one of the receptors will have to be positively selected for the cell to get the survival signals necessary for it to pass on to the next stage. Even if the other receptor does not react with self MHC this will have no effect on the cell.
B. In contrast, both receptors will have to pass the negative selection test for the T cell to survive, because if only one of them fails it, the cell will die.
C. Yes. Imagine this situation. The T cell with dual specificity could be activated appropriately during a genuine infection by a professional antigen-presenting cell plus foreign antigen 1 using T-cell receptor 1. But that same T cell, because it is now an activated effector T cell, would also be able to respond to a second peptide, which might be a self peptide, using T-cell receptor 2, without requiring the co-stimulatory signals that only professional antigen-presenting cells deliver. Thus it could cause a reaction against a self tissue, either directly, if it is a CD8 cytotoxic T cell, or indirectly, if it is a CD4 T cell, by activating potentially autoreactive B cells.
Furthermore, interferon-γ produced in the response against foreign antigen 1 could activate nonprofessional antigen-presenting cells nearby, inducing the expression of MHC class II with presentation of the self peptide above. Effector T cells with T-cell receptor 2 could make an autoimmune response against it.