Tracking global changes induced in the CD4 T cell receptor repertoire by immunization with a complex antigen using short stretches of CDR3 protein sequence.

The clonal theory of adaptive immunity proposes that immunological responses are encoded by increases in the frequency of lymphocytes carrying antigen-specific receptors. In this study, we measure the frequency of different TcRs in CD4+ T cell populations of mice immunized with a complex antigen, killed Mycobacterium tuberculosis, using high throughput parallel sequencing of the TcR beta chain. In order to track the changes induced by immunisation within this very heterogeneous repertoire, the sequence data were classified by counting the frequency of different clusters of short (3 or 4) continuous stretches of amino acids within the CDR3 repertoire of different mice. Both unsupervised (hier