Ma. Gavin et Mj. Bevan, INCREASED PEPTIDE PROMISCUITY PROVIDES A RATIONALE FOR THE LACK OF N-REGIONS IN THE NEONATAL T-CELL REPERTOIRE, Immunity, 3(6), 1995, pp. 793-800
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.