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An Incremental Increase in the Complexity of Peptides Bound to Class II MHC Changes the Diversity of Positively Selected TCRs

Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA 30912

Positive selection of the normal repertoire of TCRs results from low-avidity interactions with a set of self-peptides bound to the MHC molecules expressed 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 select different TCRs expressing a common transgenic TCR-chain and endogenous TCR-chains. Simultaneous expression of both A^b-peptide complexes changed the diversity of positively selected TCRs, indicating an additive and possibly synergistic effect of various peptides in this process.

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