Models and methods for analysis of lymphocyte repertoire generation, development, selection and evolution

Ramit Mehr, Michal Sternberg-Simon, Miri Michaeli, Yishai Pickman

Research output: Contribution to journalReview articlepeer-review

26 Scopus citations

Abstract

T and B cell receptor repertoires are diversified by variable region gene rearrangement and selected based on functionality and lack of self-reactivity. Repertoires can also be defined based on phenotype and function rather than receptor specificity - such as the diversity of T helper cell subsets. Natural killer (NK) cell repertoires, in which each cell expresses a randomly chosen subset of its inhibitory receptor genes, and is educated based on self-MHC recognition by yet unknown mechanisms, are also phenotypic repertoires. Studying the generation, development and selection of lymphocyte repertoires, and their functions during immune responses, is essential for understanding the function of the immune system in healthy individuals and in immune deficient, autoimmune or cancer patients. The study of lymphocyte repertoires will enable clinical immunologists to develop better therapeutic monoclonal antibodies, vaccines, transplantation donor-recipient matching protocols, and other immune intervention strategies. The recent development of high-throughput methods for repertoire data collection - from multicolor flow cytometry through single-cell imaging to deep sequencing - presents us now, for the first time, with the ability to analyze and compare large samples of lymphocyte repertoires in health, aging and disease. The exponential growth of these datasets, however, challenges the theoretical immunology community to develop methods for data organization and analysis. Furthermore, the need to test hypotheses regarding immune function, and generate predictions regarding the outcomes of medical interventions, necessitates the development of complex mathematical and computational models, covering processes on multiple scales, from the genetic and molecular to the cellular and system scales.

Original languageEnglish
Pages (from-to)11-22
Number of pages12
JournalImmunology Letters
Volume148
Issue number1
DOIs
StatePublished - Nov 2012

Bibliographical note

Funding Information:
The studies in our lab that are described in this review were funded over the years by The Israel Science Foundation (grant numbers 759/01 , 546/05 and 270/09 ); The Human Frontiers Science Program – a Young Investigator Grant and a Research Grant; The Israel Cancer Research Fund , The Israel Cancer Association , and a Systems Biology Prize grant from Teva Pharmaceuticals . The collaborative work on NK cells with groups in Sweden was supported by the Swedish Foundation for Strategic Research and the Swedish Research Council.

Keywords

  • B cell receptor
  • Computer simulations
  • High-throughput sequencing
  • Immunoglobulin
  • Lymphocyte repertoires
  • Mathematical models
  • Natural killer cell
  • T cell receptor

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