Conventional CD8+ and CD4+ T cells recognize antigens, presented by antigen-presenting cells in the form of short peptides loaded onto major histocompatibility complex (MHC) class I and class II
molecules, through their T cell receptor (TCR). Somatic gene rearrangement of the TCR locus and randomization of TCR hyper-variable regions generate the marked diversity of TCRs. Once
assembled, the heterodimeric TCR confers specificity to naïve T cells. The naïve T cell repertoire of an individual is established by selection processes in the thymus and cannot be broadened upon
antigen recognition by additional somatic mutations. In humans, the estimated number of distinct TCRs in the naïve T cell pool is several orders of magnitude lower than the possible array of peptides
that can be generated and accommodated into an MHC molecule. This challenge can be overcome by T cell cross-reactivity, that is the ability of a single TCR to bind multiple peptide-MHC complexes.
T-cell cross-reactivity can have both positive and negative consequences. First, it allows for covering
a wide range of foreign peptides with a limited repertoire of T cells. Second, it facilitates polyclonal immune responses to a single peptide and increases resistance to escape mutations. Third, it can induce heterologous immunity, that is the generation of memory to a pathogen different from the one against which the immune response has been originally raised. On the contrary, a negative consequence of T-cell cross-reactivity is the possibility of self-antigen recognition, potentially causing autoimmunity. The lower activation threshold of memory T-cells compared to naïve T-cells increases this risk, partially eluding the thymic negative selection checkpoint. Moreover,
heterologous immunity can be detrimental when the type of memory T-cell polarization induced by the first pathogen is inappropriate to control the second pathogen.
Thus, a better understanding of the processes and principles associated with T-cell activation, specificity, and cross-reactivity may have relevant implications in the prevention and treatment of
autoimmune diseases, the development of vaccines, and the optimization of engineered TCRs targeting tumor antigens.
This Research Topic aims to offer an overview of recent advances in the field of T-cell cross-reactivity and to provide novel insights into the mechanisms governing this phenomenon.
These may include, but are not limited to:
- Protective and pathogenic heterologous immunity and implications for vaccine development
- Molecular mimicry and autoimmunity
- Modelling of TCR binding degeneracy
- Regulation of T cell sensitivity to antigen stimulation
- Correlation between T cell sensitivity and bystander activation
- Assessment of naïve and memory TCR repertoires complexity and specificity
- Mechanisms of immune-synapse formation, TCR activation, and signaling
- Precision medicine approaches for autoimmune diseases and cancer
- Insights about cross-reactive non-conventional T-cells
Accepted manuscripts will include original articles, brief research reports, reviews, mini-reviews, methods, and hypotheses and theories.
Conventional CD8+ and CD4+ T cells recognize antigens, presented by antigen-presenting cells in the form of short peptides loaded onto major histocompatibility complex (MHC) class I and class II
molecules, through their T cell receptor (TCR). Somatic gene rearrangement of the TCR locus and randomization of TCR hyper-variable regions generate the marked diversity of TCRs. Once
assembled, the heterodimeric TCR confers specificity to naïve T cells. The naïve T cell repertoire of an individual is established by selection processes in the thymus and cannot be broadened upon
antigen recognition by additional somatic mutations. In humans, the estimated number of distinct TCRs in the naïve T cell pool is several orders of magnitude lower than the possible array of peptides
that can be generated and accommodated into an MHC molecule. This challenge can be overcome by T cell cross-reactivity, that is the ability of a single TCR to bind multiple peptide-MHC complexes.
T-cell cross-reactivity can have both positive and negative consequences. First, it allows for covering
a wide range of foreign peptides with a limited repertoire of T cells. Second, it facilitates polyclonal immune responses to a single peptide and increases resistance to escape mutations. Third, it can induce heterologous immunity, that is the generation of memory to a pathogen different from the one against which the immune response has been originally raised. On the contrary, a negative consequence of T-cell cross-reactivity is the possibility of self-antigen recognition, potentially causing autoimmunity. The lower activation threshold of memory T-cells compared to naïve T-cells increases this risk, partially eluding the thymic negative selection checkpoint. Moreover,
heterologous immunity can be detrimental when the type of memory T-cell polarization induced by the first pathogen is inappropriate to control the second pathogen.
Thus, a better understanding of the processes and principles associated with T-cell activation, specificity, and cross-reactivity may have relevant implications in the prevention and treatment of
autoimmune diseases, the development of vaccines, and the optimization of engineered TCRs targeting tumor antigens.
This Research Topic aims to offer an overview of recent advances in the field of T-cell cross-reactivity and to provide novel insights into the mechanisms governing this phenomenon.
These may include, but are not limited to:
- Protective and pathogenic heterologous immunity and implications for vaccine development
- Molecular mimicry and autoimmunity
- Modelling of TCR binding degeneracy
- Regulation of T cell sensitivity to antigen stimulation
- Correlation between T cell sensitivity and bystander activation
- Assessment of naïve and memory TCR repertoires complexity and specificity
- Mechanisms of immune-synapse formation, TCR activation, and signaling
- Precision medicine approaches for autoimmune diseases and cancer
- Insights about cross-reactive non-conventional T-cells
Accepted manuscripts will include original articles, brief research reports, reviews, mini-reviews, methods, and hypotheses and theories.