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The adaptive immune system is a natural diagnostic and therapeutic. Itrecognizes threats earlier than clinical symptoms manifest and neutralizesantigen with exquisite specificity. Recognition specificity and broadreactivity is enabled via adaptive B- and T-cell receptors: the immune receptorrepertoire. The human immune system, however, is not omnipotent. Our naturaldefense system sometimes loses the battle to parasites and microbes and eventurns against us in the case of cancer, autoimmune and inflammatory disease. Along-standing dream of immunoengineers has been, therefore, to mechanisticallyunderstand how the immune system sees, reacts and remembers antigens. Only veryrecently, experimental and computational methods have achieved sufficientquantitative resolution to start querying and engineering adaptive immunitywith great precision. In specific, these innovations have been applied with thegreatest fervency and success in immunotherapy, autoimmunity and vaccinedesign. The work here highlights advances, challenges and future directions ofquantitative approaches which seek to advance the fundamental understanding ofimmunological phenomena, and reverse engineer the immune system to produceauspicious biopharmaceutical drugs and immunodiagnostics. Our review indicatesthat the merger of fundamental immunology, computational immunology anddigital-biotechnology minimizes black box engineering, thereby advancing bothimmunological knowledge and as well immunoengineering methodologies.

Augmenting adaptive immunity: progress and challenges in the quantitative engineering and analysis of adaptive immune receptor repertoires