Autoreactivity of T cells from nonobese diabetic mice: An I-Ag7-dependent reaction

Osami Kanagawa, Steven M. Martin, Barbara A. Vaupel, Eugenio Carrasco-Marin, Emil R. Unanue

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Mice bearing the I-Ag7 class II major histocompatibility complex molecules contain a high number of spontaneous autoreactive T cells, as estimated by limiting-dilution assays. We found this autoreactivity in various strains that bear the I-Ag7 molecule, such as the nonobese diabetic (NOD) mouse strain, which spontaneously develops autoimmune diabetes. However, NOD mice strains that do not express the I-Ag7 molecule, but instead express I-Ab, do not have a high incidence of autoreactive T cells. About 15% of the autoreactive T cells also recognize the I-Ag7 molecule expressed in the T2 line, which is defective in the processing of protein antigens. We interpret this to mean that some of the T cells may interact with class II molecules that are either devoid of peptides or contain a limited peptide content. We also find a high component of autoreactivity among antigenspecific T cell clones. These T cell clones proliferate specifically to protein antigens but also have a high level of reactivity to antigen-presenting cells not pulsed with antigen. Thus, the library of T cell receptors in NOD mice is skewed to autoreactivity, which we speculate is based on the weak peptidebinding properties of I-Ag7 molecules.

Original languageEnglish
Pages (from-to)1721-1724
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number4
DOIs
StatePublished - Feb 17 1998

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