Allelic exclusion of {alpha} chains in TCRs

Although the ß chains of ß⁺ T cells exhibitallelic exclusion it has recently been shown that 20–30%of such cells express both chain alleles on their surface.Potentially these cells have dual specificity, and it has beensuggested that they may play a role in autoimmunity and alloreactlvtty.The analysis presented in this paper examines critically thepossibility that the observed violation of allelic exclusionof chain expression arises as a natural consequence of a chainrearrangement and intrathymlc positive selection. It is concludedthat, subject to certain identified conditions being satisfied,the observed frequency of T cells expressing two chains iscompatible with such a mechanism. However, It is an essentialassumption of the theory that, of the two ß chaincomplexes on these cells, only one mediates positive selection.It follows that to what extent both receptors are actually functionaldepends on whether an ß chain complex that has failedto satisfy the criterion of positive selection can mediate antigenrecognition in the periphery. In principle the answer to thisquestion may be different if one is considering autoreactlvltyor alloreactlvlty. Finally, attention is drawn to the apparentdiscrepancy between the frequency of peripheral T cells expressingtwo chains and the failure to find T cell clones of this phenotype.Possible explanations are discussed.