Clustering and Annotation of T Cell Receptor Repertoires

Immunological protection against a wide variety of pathogens is largely mediated by the diverse and dynamic T cell receptor (TCR) repertoire, a crucial component of the adaptive immune system. An encounter with infectious agents stimulates specific T cells to initiate a direct immune response to combat intruders. Hence, the TCR repertoire may conceal crucial information regarding current and past infections and might assist in the development and monitoring of vaccines. To unlock its knowledge, we describe a computational workflow involving both supervised and unsupervised machine learning techniques to analyze and annotate full TCR repertoire data. The method is explained using data from a published yellow fever virus (YFV) vaccination study in healthy individuals. The TCR repertoire of one individual is studied before and 2 weeks after vaccination, using an efficient clustering method and identification of YFV-specific TCRs.