Analyses of the TCR repertoire of MHC class II-restricted innate CD4⁺ T cells.

Analysis of the T-cell receptor (TCR) repertoire of innate CD4(+) T cells selected by major histocompatibility complex (MHC) class II-dependent thymocyte-thymocyte (T-T) interaction (T-T CD4(+) T cells) is essential for predicting the characteristics of the antigens that bind to these T cells and for distinguishing T-T CD4(+) T cells from other types of innate T cells. Using the TCR(mini) Tg mouse model, we show that the repertoire of TCRα chains in T-T CD4(+) T cells was extremely diverse, in contrast to the repertoires previously described for other types of innate T cells. The TCRα chain sequences significantly overlapped between T-T CD4(+) T cells and conventional CD4(+) T cells in the thymus and spleen. However, the diversity of the TCRα repertoire of T-T CD4(+) T cells seemed to be restricted compared with that of conventional CD4(+) T cells. Interestingly, the frequency of the parental OT-II TCRα chains was significantly reduced in the process of T-T interaction. This diverse and shifted repertoire in T-T CD4(+) T cells has biological relevance in terms of defense against diverse pathogens and a possible regulatory role during peripheral T-T interaction.