Early establishment of diverse T cell receptor profiles for influenza-specific CD8+CD62Lhi memory T cells

Single-cell analysis of endogenous, primary CD8(+) T cell responses to the influenza (DNP366)-N-b and D(b)PA(224) epitopes indicates that prominent clonotypes bearing public or shared T cell receptors (TCRs) subset early into CD62L(hi) and CD62L(lo) populations. The CD62L(lo) effectors divide more and are rapidly eliminated during the contraction phase, whereas stable CD62Lhi memory populations persist in the long-term. Reflecting the high frequency of small CD62Lhi clones expressing private TCRs, the TCR diversity range per mouse is generally two times higher within the CD62L(hi)CD8(+)D(b)NP(366)(+) set (1.6 times higher for CD62L(hi)CD8(+)DbPA(224)(+)) from 8 to > 180 days after antigen challenge. Memory CD8(+)CD62L(hi) T cell precursors thus segregate from the outset into populations expressing best-fit and suboptimal TCR characteristics, with this pattern being maintained stably thereafter. Hence, our analysis suggests that early establishment of influenza-specific memory within the CD8(+)CD62L(hi) subset preserves clonal diversity and prevents overdominance by a few public, or shared, clones.