Conserved T cell receptor usage in primary and recall responses to an immunodominant influenza virus nucleoprotein epitope

The CD8 ⁺ T cell response to the immunodominant D ^b NP ₃₆₆ epitope has been analyzed sequentially to determine the prevalence and persistence of different T cell antigen receptor (TCR)Vβ8.3 clonotypes after primary and secondary influenza virus challenge. Based on the length and amino acid sequences of the complementarity-determining region 3 of TCRβ (CDR3β) loop and associated Jβ usage, the same dominant TCRβ signatures were found in the blood, the spleen, and the site of virus-induced pathology in the infected respiratory tract. Longitudinal analysis demonstrated that TCRβ prominent in the antigen-driven phase of response persisted into memory and were again expanded after secondary challenge. A proportion of these high-frequency TCRβ expressed "public" CDR3β sequences that were detected in every mouse sampled, whereas others were found more than once but were not invariably present. Analysis of N-region nucleotide diversity established that as many as 10 different nucleic acid sequences (maximum of four "nucleotypes" in any one mouse) could encode a single public TCRβ amino acid sequence. Conversely, whereas some of the unique, "private" TCRβ achieved a substantial clone size, they were always specified by a single nucleotype. Although there is a strong stochastic element in this response, the public TCRβ seem to represent a "best fit" for this immunodominant epitope, are selected preferentially from the naive TCR repertoire, and assume even greater prominence after secondary challenge.