Getting started with immunology and adaptive immune receptors

Note

Aim: provide basic introduction and references in the field of adaptive immune receptors and repertoires

Level: beginner 🌱

The immune system protects the organism against pathogens, such as viruses or bacteria, but also the organism’s own malicious cells, in cases such as cancer. The immune system relies on two mechanisms for this purpose: (i) innate immunity in charge of the immediate response and (ii) adaptive immunity, mounting a slower but a more specific response.

The adaptive immune system includes B- and T-cells and their receptors that recognize the pathogens. These immune receptors consist of two paired sequences (two chains) of amino acids which are highly diverse, and highly specific towards certain pathogens. In the case of B-cell receptors (BCRs, also called antibodies when secreted), there are two symmetric heavy and light chains in the receptor, while the T-cell receptor (TCR) consists of an alpha (α) and a beta (β) chain. The chains in both B- and T-cell receptors include a hypervariable region called complementarity determining region 3 (CDR3, a sequence between 5 and 20 amino acids long), which is believed to be the most significant for recognition of the pathogen. The set of all immune receptors in an individual is called the immune repertoire, that keeps receptors specific to previously encountered pathogens so that it can quickly respond upon reinfection. In this manner, the immune repertoire records all past and present treats, thus allowing for diagnostics development based on the repertoire analysis.

Relevant reviews:

  • Brown, A. J. et al. Augmenting adaptive immunity: progress and challenges in the quantitative engineering and analysis of adaptive immune receptor repertoires. Mol. Syst. Des. Eng. 4, 701–736 (2019).

  • Greiff, V., Yaari, G. & Cowell, L. Mining adaptive immune receptor repertoires for biological and clinical information using machine learning. Current Opinion in Systems Biology (2020) doi:10.1016/j.coisb.2020.10.010.

  • Arnaout, R. A. et al. The Future of Blood Testing Is the Immunome. Front. Immunol. 12, (2021).

  • Davis, M., Tato, C. & Furman, D. Systems immunology: just getting started. Nat Immunol 18, 725–732 (2017).

  • Georgiou, G., Ippolito, G., Beausang, J. et al. The promise and challenge of high-throughput sequencing of the antibody repertoire. Nat Biotechnol 32, 158–168 (2014).

Relevant books:

  • Janeway’s immunobiology, by Kenneth Murray and Casey Weaver, ISBN: 978-0-815-34505-3

  • Basic immunology: Functions and disorders of the immune system, by Abul K. Abbas, Andrew H. Lichtman, and Shiv Pillai, ISBN: 9780323549431

Other resources: