Antigen‐specific and cross‐reactive T cells in protection and disease

Abstract

Human T cells have a diverse T-cell receptor (TCR) repertoire that endows them with the ability to identify and defend against a broad spectrum of antigens. The universe of possible antigens that T cells may encounter, however, is even larger. To effectively surveil such a vast universe, the T-cell repertoire must adopt a high degree of crossreactivity. Likewise, antigen-specific and cross-reactive T-cell responses play pivotal roles in both protective and pathological immune responses in numerous diseases. In this review, we explore the implications of these antigen-driven T-cell responses, with a particular focus on CD8+ T cells, using infection, neurodegeneration, and cancer as examples. We also summarize recent technological advances that facilitate highthroughput profiling of antigen-specific and cross-reactive T-cell responses experimentally, as well as computational biology approaches that predict these interactions.

Landscape of T cell epitopes displays hot mutations of SARS‐CoV‐2 variant spikes evading cellular immunity

“…Cross‐reactive T cell responses play decisive roles in evaluating the appropriate vaccine target for protection against infection with viral variants 29 . To assess cross‐T cell responses among DNA vaccines, T cell responses to SARS‐CoV‐2 spike proteins from PS and different VOCs were measured in the splenocytes of vaccinated mice using murine IFN‐γ Elispot kits (Figure 1D).…”

Potential clinical implications of molecular mimicry‐induced autoimmunity

“…Identifying immunodominant T cell epitopes on myocarditic viruses and their homologous cardiac antigens could enable antigen‐specific immunotherapy to selectively tolerize those cross‐reactive T cells 110 . Determining susceptibilities like HLA associations may help personalize antigen‐specific prevention or treatment based on an individual's molecular mimicry risk 111 …”

Editorial: T cell specificity and cross-reactivity – implications in physiology and pathology

“…This deficit in TCR diversity is resolved by T cell cross-reactivity, that is the ability of a single TCR to bind multiple peptide-MHC complexes, albeit with different affinities. In addition to the theoretical need, numerous independent studies have experimentally demonstrated the existence of cross-reactive T cells [reviewed in ( 9 , 10 )].…”