Quantifying T Cell Cross-Reactivity: Influenza and Coronaviruses

Viruses. 2021 Sep 7;13(9):1786. doi: 10.3390/v13091786.

Abstract

If viral strains are sufficiently similar in their immunodominant epitopes, then populations of cross-reactive T cells may be boosted by exposure to one strain and provide protection against infection by another at a later date. This type of pre-existing immunity may be important in the adaptive immune response to influenza and to coronaviruses. Patterns of recognition of epitopes by T cell clonotypes (a set of cells sharing the same T cell receptor) are represented as edges on a bipartite network. We describe different methods of constructing bipartite networks that exhibit cross-reactivity, and the dynamics of the T cell repertoire in conditions of homeostasis, infection and re-infection. Cross-reactivity may arise simply by chance, or because immunodominant epitopes of different strains are structurally similar. We introduce a circular space of epitopes, so that T cell cross-reactivity is a quantitative measure of the overlap between clonotypes that recognize similar (that is, close in epitope space) epitopes.

Keywords: bipartite network; competition process; cross-reactivity; heterologous infection; mathematical modeling; pre-existing immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Coronavirus / classification
  • Coronavirus / genetics
  • Coronavirus / immunology*
  • Coronavirus Infections / immunology*
  • Cross Reactions / immunology*
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunodominant Epitopes / immunology*
  • Immunologic Memory
  • Influenza A virus / genetics
  • Influenza A virus / immunology*
  • Influenza, Human / immunology
  • Mice
  • Models, Theoretical
  • Orthomyxoviridae Infections / immunology
  • Receptors, Antigen, T-Cell

Substances

  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Receptors, Antigen, T-Cell