Figure 7. The evolving concepts of the relationship between positively selecting self-peptide and post-selection T cell repertoire.
The figures show the progress of our understanding about the relationship between thymic self-peptides and post-selection CD4+ T cell repertoire, and are arranged in chorological order. The first finding from late 90′ revealed that one positively selecting self-peptide was capable of selecting many different TCRs (Ignatowicz et al., 1996; Ignatowicz et al., 1997; Liu et al., 1997; Huseby et al., 2005). A few years later, Barton and Rudensky proposed that even though one self-peptide may select many TCRs, a diverse low abundant self-peptide repertoire is required to generate a full TCR repertoire (Barton and Rudensky, 1999). Subsequently, with the publication of a series of single chain mice, the model was further refined because even though the TCR repertoire selected by one single ligand was not reduced significantly enough to allow an visualization of a repertoire ‘hole’, the postselection T cells in each single chain mouse showed different degrees of self-peptide reactivity in mixed lymphocyte culture (Barton et al., 2002). These studies showed that a diverse collection of positively selecting self-peptides were necessary to generate a full T cell repertoire (Barton and Rudensky, 1999; Barton et al., 2002). This present study involving the gp250 self-peptide showed increased frequency of Vα11+Vβ3+ CD4+ T cells with MCC-preferred CDR3 features in gp250 SC mice. The Vα11+Vβ3+ CD4+ T cells with specific CDR3 features were the dominant responders to promote MCC primary and memory responses. Therefore, gp250’s selecting capability provided a possible explanation to elucidate Vα11+ TCR-driven MCC immunodominance: a positively selecting self-peptide may favor the selection of TCR pairs and CDR3 features that were specific for MCC responses.