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Journal Article
Why must T cells be cross-reactive?
2012
Overview
T cells must recognize a vast array of potential foreign peptide–MHC complexes. Comprehensive immune cover can only be provided if each T cell recognizes numerous peptides. The implications of this T cell cross-reactivity include autoimmune disease but also provide opportunities for multiple therapeutic interventions.
Clonal selection theory proposed that individual T cells are specific for a single peptide–MHC antigen. However, the repertoire of αβ T cell receptors (TCRs) is dwarfed by the vast array of potential foreign peptide–MHC complexes, and a comprehensive system requires each T cell to recognize numerous peptides and thus be cross-reactive. This compromise on specificity has profound implications because the chance of any natural peptide–MHC ligand being an optimal fit for its cognate TCR is small, as there will almost always be more-potent agonists. Furthermore, any TCR raised against a specific peptide–MHC complex
in vivo
can only be the best available solution from the naive T cell pool and is unlikely to be the best possible solution from the substantially greater number of TCRs that could theoretically be produced. This 'systems view' of TCR recognition provides a plausible cause for autoimmune disease and substantial scope for multiple therapeutic interventions.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antigens
/ Biomedical and Life Sciences
/ Cross Reactions - immunology
/ Dopamine
/ Genes
/ Humans
/ Major histocompatibility complex
/ Major Histocompatibility Complex - genetics
/ Major Histocompatibility Complex - immunology
/ Memory
/ Peptides
/ Protein Binding - immunology
/ Receptors, Antigen, T-Cell - genetics
/ Receptors, Antigen, T-Cell - immunology
/ T cells
