Avidity maturation of memory CD8 T cells is limited by self-antigen expression
Graduate School of Biomedical Sciences; Department of Immunology
Medical Subject Headings
Animals; Autoantigens; Autoimmunity; CD8-Positive T-Lymphocytes; Cell Differentiation; Cross Reactions; Female; Immune Tolerance; *Immunologic Memory; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Ovalbumin; Peptide Fragments; Self Tolerance; Transcription Factors; Vesicular stomatitis Indiana virus
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.
Rights and Permissions
Citation: J Exp Med. 2008 Aug 4;205(8):1859-68. Epub 2008 Jul 14. Link to article on publisher's site
DOI of Published Version
The Journal of experimental medicine
Turner, Michael J.; Jellison, Evan Robert; Lingenheld, Elizabeth G.; Puddington, Lynn; and Lefrancois, Leo, "Avidity maturation of memory CD8 T cells is limited by self-antigen expression" (2008). GSBS Student Publications. 1539.