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

TL;DR

This paper reviews recent advances in quantitative methods for analyzing and engineering adaptive immune receptor repertoires, highlighting progress, challenges, and future directions in immunology and immunoengineering.

Contribution

It synthesizes recent developments in experimental and computational techniques for understanding and manipulating adaptive immunity, emphasizing their application in immunotherapy, autoimmunity, and vaccine design.

Findings

Quantitative methods have achieved high resolution in immune repertoire analysis.

Integration of immunology and digital biotechnology enhances understanding and engineering of immune responses.

Recent innovations have improved immunotherapy and vaccine development.

Abstract

The adaptive immune system is a natural diagnostic and therapeutic. It recognizes threats earlier than clinical symptoms manifest and neutralizes antigen with exquisite specificity. Recognition specificity and broad reactivity is enabled via adaptive B- and T-cell receptors: the immune receptor repertoire. The human immune system, however, is not omnipotent. Our natural defense system sometimes loses the battle to parasites and microbes and even turns against us in the case of cancer, autoimmune and inflammatory disease. A long-standing dream of immunoengineers has been, therefore, to mechanistically understand how the immune system sees, reacts and remembers antigens. Only very recently, experimental and computational methods have achieved sufficient quantitative resolution to start querying and engineering adaptive immunity with great precision. In specific, these innovations have been applied with the greatest fervency and success in immunotherapy, autoimmunity and vaccine design. The work here highlights advances, challenges and future directions of quantitative approaches which seek to advance the fundamental understanding of immunological phenomena, and reverse engineer the immune system to produce auspicious biopharmaceutical drugs and immunodiagnostics. Our review indicates that the merger of fundamental immunology, computational immunology and digital-biotechnology minimizes black box engineering, thereby advancing both immunological knowledge and as well immunoengineering methodologies.