Quantifying T Cell Cross-Reactivity: Influenza and Coronaviruses

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.

Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns

“…Pre-existing immunity is not only reflected in the presence of pre-vaccination HI titers, but also influenza-specific cross-reactive T-cells are of importance 24 . To fully understand the effect of pre-existing immunity on subsequent QIV responsiveness, future research should additionally investigate QIV-specific T-cell immunity.…”

Quantification of heterogeneity in human CD8+T cell responses to vaccine antigens: an HLA-guided perspective

“…Yet, we still do not have a single metric to define protective T cell immune responses. This is a huge challenge given the phenotypic and multi-functional heterogeneity of T cell responses, and TCR diversity and cross-reactivity [39, 14].…”

“…Figure reproduced from Ref. [14] (Figure 1) with permission under the terms and conditions of the Creative Commons Attribution license CC BY 4.0.…”

Cross-reactivity influences changes in human influenza A virus and Epstein Barr virus specific CD8 memory T cell receptor alpha and beta repertoires between young and old

“…Methods to predict optimum TCR features to be recognized and activated by a particular antigen and for identifying TCR antigen-specificity groups without the need to isolate antigen-specific T cells would be highly valuable and are beginning to be developed (6,29). Recently, progress has been made in developing algorithms that identify crossreactive epitopes, between strains of similar viruses like IAV and coronaviruses (58).…”