The Journal of Immunology, Vol 141, Issue 12 4124-4128, Copyright © 1988 by American Association of Immunologists

ARTICLES

T cell recognition of bovine ribonuclease. Self/non-self discrimination at the level of binding to the I-Ak molecule

RG Lorenz, AN Tyler and PM Allen
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.

Bovine RNase A specific T-cell hybridomas were generated to study the recognition of foreign Ag by T lymphocytes. One hybrid, TS12, was shown to recognize RNase in association with I-Ak. This hybridoma required bovine RNase to be processed before recognition. The immunogenic determinant on the RNase molecule recognized by TS12 was localized to the tryptic fragment RNase(40-61). All of the stimulatory ability of this determinant was shown to be contained within the synthetic 14mer RNase(43-56). When this segment of bovine RNase was compared with the self murine sequence, only one amino acid difference was found, a substitution of a proline residue at position 50 for a serine residue. This substitution completely abolishes binding to the I-Ak molecule, as shown by both functional and direct binding assays. This finding shows that self/non-self discrimination not only occurs at the level of the T cell, but also can be caused by an inability of the self peptide to associate with a class II molecule.

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