In vivo selection of a TCR V repertoire directed against an immunodominant influenza virus CTL epitope

Abstract

Little is known about the mechanisms governing TCR repertoire selection in response to foreign antigens. Here, we evaluate the molecular features of the murine C57BL/6 (B6) TCR Vβ repertoire directed at the NP_366–374 immunodominant epitope of the influenza virus nucleoprotein. Common or ‘public’ β chains are shared among individuals following either primary or secondary infection. Importantly, repertoire diversity decreases substantially after a second viral exposure due to enrichment of TCRs sharing Vβ CDR3 loops of identical length and highly related amino acid sequences. TCRs from these secondary T cell populations possess greater overall avidity for the NP_366–374/D^b complex compared to those from the primary repertoire. Thus, expansion of CD8⁺ T cells expressing a favored germline Vβ gene segment in the primary response and further selection for CDR3β loops during the secondary response, contribute to optimization of immune recognition against certain viral epitopes.