Role of self-peptides in positively selecting the T-cell repertoire

The fate of an immature thymocyte is determined by the specificity of its alpha beta T-cell receptor. Only cells expressing receptors that interact with sufficient affinity with major histocompatibility complex (MHC) molecules expressed on thymus epithelial cells are positively selected and go on to mature and seed the peripheral lymphoid organs. The H-2Kb class-I MHC molecule positively selects for the maturation of cytotoxic T lymphocytes that will respond in the periphery to H-2Kb cells presenting a foreign peptide. We have now analysed the ability of variant H-2Kb molecules to positively select T-cells that respond to H-2Kb with ovalbumin. Our results indicate that self-peptides, presented in the groove of the class-I molecule on thymus epithelial cells, are critically involved in positive selection of the T-cell repertoire. Furthermore, the ability of four different H-2Kb variants to select this response in the thymus correlates with their ability to present the ovalbumin peptide, indicating that a self-peptide mimic of the foreign peptide could be involved in positive selection.