| First Author | Holst J | Year | 2008 |
| Journal | Nat Immunol | Volume | 9 |
| Issue | 6 | Pages | 658-66 |
| PubMed ID | 18469818 | Mgi Jnum | J:136207 |
| Mgi Id | MGI:3795631 | Doi | 10.1038/ni.1611 |
| Citation | Holst J, et al. (2008) Scalable signaling mediated by T cell antigen receptor-CD3 ITAMs ensures effective negative selection and prevents autoimmunity. Nat Immunol 9(6):658-66 |
| abstractText | The T cell antigen receptor (TCR)-CD3 complex is unique in having ten cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). The physiological importance of this high TCR ITAM number is unclear. Here we generated 25 groups of mice expressing various combinations of wild-type and mutant ITAMs in TCR-CD3 complexes. Mice with fewer than seven wild-type CD3 ITAMs developed a lethal, multiorgan autoimmune disease caused by a breakdown in central rather than peripheral tolerance. Although there was a linear correlation between the number of wild-type CD3 ITAMs and T cell proliferation, cytokine production was unaffected by ITAM number. Thus, high ITAM number provides scalable signaling that can modulate proliferation yet ensure effective negative selection and prevention of autoimmunity. |
