INCREASED PEPTIDE PROMISCUITY PROVIDES A RATIONALE FOR THE LACK OF N-REGIONS IN THE NEONATAL T-CELL REPERTOIRE

Making use of mice deficient for terminal deoxynucleotidyl transferase (TdT) expression and a random peptide library, we have examined the d iversity and peptide specificity of the neonatal T cell repertoire spe cific for a single H-2D(b)-restricted peptide. Consistent with the pre dicted decrease in repertoire diversity, polyclonal CTL lines and indi vidual clones from different TdT(0) mice are more similar to each othe r than those from different wild-type mice in terms of their fingerpri nts of cross-reactivity to the library and their TCR sequences. We hav e also found that several TdT(0) CTL clones cross-react with many more library peptides than wild-type CTL clones. In a few instances, the d egree of peptide promiscuity correlates with TCR sequence characterist ics such as N region addition and homology-directed recombination, but not CDR3 loop length. Based on epitope titrations for each clone, TCR affinity for antigen is consistently high; thus, this reduced specifi city for peptide may coincide with an accentuated affinity for the alp ha helices of the MHC. Peptide promiscuity in the neonate may allow th e relatively small numbers of T cells in the periphery to protect agai nst a broader range of pathogens.