An incremental increase in the complexity of peptides bound to class II MHC changes the diversity of positively selected alpha beta TCRs

Positive selection of the normal repertoire of TCRs results from low-avidit y interactions with a set of self-peptides bound to the MHC molecules expre ssed by thymic epithelial cells. The contribution of the individual peptide to positive selection remains a matter of debate. Here, for the first time , we show that two covalent class II MHC-peptide complexes positively selec t different TCRs expressing a common transgenic TCR beta -chain and endogen ous TCR alpha -chains. Simultaneous expression of both A(b)-peptide complex es changed the diversity of positively selected TCRs, indicating an additiv e and possibly synergistic effect of various peptides in this process.