Abstract
AbstractDiverse T and B cell repertoires play an important role in mounting effective immune responses against a wide range of pathogens and malignant cells. The number of unique T and B cell clones is characterized by T and B cell receptors (TCRs and BCRs), respectively. Although receptor sequences are generated probabilistically by recombination processes, clinical studies found a high degree of sharing of TCRs and BCRs among different individuals. In this work, we use a general probabilistic model for T/B cell receptor clone abundances to define “publicness” or “privateness” and information-theoretic measures for comparing the frequency of sampled sequences observed across different individuals. We derive mathematical formulae to quantify the mean and the variances of clone richness and overlap. Our results can be used to evaluate the effect of different sampling protocols on abundances of clones within an individual as well as the commonality of clones across individuals. Using synthetic and empirical TCR amino acid sequence data, we perform simulations to study expected clonal commonalities across multiple individuals. Based on our formulae, we compare these simulated results with the analytically predicted mean and variances of the repertoire overlap. Complementing the results on simulated repertoires, we derive explicit expressions for the richness and its uncertainty for specific, single-parameter truncated power-law probability distributions. Finally, the information loss associated with grouping together certain receptor sequences, as is done in spectratyping, is also evaluated. Our approach can be, in principle, applied under more general and mechanistically realistic clone generation models.
Funder
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Army Research Office
Foundation for the National Institutes of Health
National Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
Computational Theory and Mathematics,General Agricultural and Biological Sciences,Pharmacology,General Environmental Science,General Biochemistry, Genetics and Molecular Biology,General Mathematics,Immunology,General Neuroscience
Reference59 articles.
1. Abbas AK, Lichtman AH, Pillai S (2021) Cellular and molecular immunology, 10th edn. South Asia Edition, Elsevier Health Sciences, New Delhi
2. Alt FW, Oltz EM, Young F, Gorman J, Taccioli G, Chen J (1992) VDJ recombination. Immunol Today 13(8):306–314
3. Baez JC, Fritz T, Leinster T (2011) A characterization of entropy in terms of information loss. Entropy 13(11):1945–1957
4. Briney B, Inderbitzin A, Joyce C, Burton DR (2019) Commonality despite exceptional diversity in the baseline human antibody repertoire. Nature 566(7744):393–397
5. Casrouge A, Beaudoing E, Dalle S, Pannetier C, Kanellopoulos J, Kourilsky P (2000) Size estimate of the $$\alpha \beta $$ TCR repertoire of naive mouse splenocytes. J Immunol 164(11):5782–5787