The Journal of Experimental Medicine
3rd Skeletal Biology and Medicine Symposium
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Journal of Experimental Medicine, Vol 175, 545-552, Copyright © 1992 by Rockefeller University Press

ARTICLES

Identification of an autologous insulin B chain peptide as a target antigen for H-2Kb-restricted cytotoxic T lymphocytes

JM Sheil, SE Shepherd, GF Klimo and Y Paterson
Department of Microbiology and Immunology, West Virginia University Health Sciences Center, Morgantown 26506.

We have examined the CD8+ peripheral T cell repertoire of C57BL/6 (H- 2b) mice for cytotoxic T lymphocyte (CTL) reactivities to insulin, using in vitro immunization with a chymotryptic digest of reduced bovine insulin. The results presented in this study demonstrate that potentially autoreactive H-2Kb-restricted cytotoxic T cells specific for an autologous insulin B chain peptide are present in the preimmune splenic T cell repertoire. The immunogenic peptide comprises residues 7- 15 from the insulin B chain and has features in common with naturally processed Kb-restricted peptides identified by others. The minimal peptide sequence recognized by these cytotoxic T cells is 10-15, which is highly conserved in mammalian species and constitutes a self-peptide in mice. The presence of class I major histocompatibility complex- restricted CTLs with potentially autoreactive specificities in preimmune animals raises the possibility of a role for such cells in autoimmune disease states. Possible mechanisms for the in vivo expansion of insulin peptide-specific CTLs are discussed.
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