T Cell Specificity And Cross Reactivity Implications In Physiology And Pathology

Download or read book T cell specificity and Cross-reactivity – Implications in Physiology and Pathology written by Samuele Notarbartolo and published by Frontiers Media SA. This book was released on 2024-03-07 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.