Avidity maturation of memory CD8 T cells is limited by self-antigen expression

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Immunology

Publication Date


Document Type



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

Journal/Book/Conference Title

The Journal of experimental medicine

Related Resources

Link to Article in PubMed

PubMed ID