Th17 Responses to Collagen Type V, kα1-Tubulin, and Vimentin Are Present Early in Human Development and Persist Throughout Life

Th17-dependent autoimmune responses can develop after heart or lung transplantation, and are associated with fibro-obliterative forms of chronic rejection. However, the specific self-antigens involved are typically different from those associated with autoimmune disease. To investigate the basis of these responses, we questioned whether removal of Tregs or blockade of function reveals a similar auto-antigen bias. We found that Th17 cells specific for collagen type V (Col V), kα-1-tubulin, and vimentin were present in healthy, adult PBMC, cord blood, and fetal thymus. Using synthetic peptides and recombinant fragments of the Col V triple helical region (α1V), we compared Th17 cells from healthy donors with Th17 cells from Col V-reactive heart and lung patients. While the latter responded well to α1(V) fragments and peptides in a DR–restricted fashion, Th17 cells from healthy individuals responded in a DR-restricted fashion to fragments, but not to peptides. Col V, kα-1-tubulin, and vimentin are preferred targets of a highly conserved, hitherto unknown, pre-existing Th17 response that is MHCII-restricted. These data suggest that autoimmunity after heart and lung transplantation may result from dysregulation of an intrinsic mechanism controlling airway and vascular homeostasis. This article is protected by copyright. All rights reserved.