Avidity maturation of memory CD8 T cells is limited by self-antigen expression
Graduate School of Biomedical Sciences; Department of Immunology
Life Sciences | Medicine and Health Sciences
Immune tolerance to self-antigens is a complex process that utilizes multiple mechanisms working in concert to maintain homeostasis and prevent autoimmunity. We developed a system that revealed a population of self-specific CD8 T cells within the endogenous T cell repertoire. Immunization of ovalbumin (OVA)-expressing transgenic mice with recombinant viruses expressing OVA-peptide variants induced self-reactive T cells in vivo that matured into memory T cells able to respond to secondary infection. However, whereas the avidity of memory cells in normal mice increased dramatically with repeated immunizations, avidity maturation was limited for self-specific CD8 T cells. Despite decreased avidity, such memory cells afforded protection against infection, but did not induce overt autoimmunity. Further, up-regulation of self-antigen expression in dendritic cells using an inducible system promoted programmed death-1 expression, but not clonal expansion of preexisting memory cells. Thus, the self-reactive T cell repertoire is controlled by overlapping mechanisms influenced by antigen dose.
DOI of Published Version
J Exp Med. 2008 Aug 4;205(8):1859-68. Epub 2008 Jul 14. Link to article on publisher's site
The Journal of experimental medicine
Turner MJ, Jellison ER, Lingenheld EG, Puddington L, Lefrancois L. (2008). Avidity maturation of memory CD8 T cells is limited by self-antigen expression. GSBS Student Publications. https://doi.org/10.1084/jem.20072390. Retrieved from https://escholarship.umassmed.edu/gsbs_sp/1539