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

Abstract Single-cell analysis of endogenous, primary CD8+ T cell responses to the influenza DbNP366 and DbPA224 epitopes indicates that prominent clonotypes bearing “public” or “shared” T cell receptors (TCRs) subset early into CD62Lhi and CD62Llo populations. The CD62Llo 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 CD62LhiCD8+DbNP366 + set (1.6 times higher for CD62LhiCD8+DbPA224 +) from 8 to >180 days after antigen challenge. Memory CD8+CD62Lhi 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+CD62Lhi subset preserves clonal diversity and prevents “overdominance” by a few public, or shared, clones. influenza A virus T cell receptor repertoire