H–2 restriction is an established characteristic of T-cell behaviour1–3 and, in effect, it means that mouse T cells are activated against foreign antigens only if those antigens are presented in a membrane association with molecules of the mouse major histocompatibility complex, H–2. Whether T-cell inactivation or tolerance is also H–2-restricted is a question which has been tested directly4–5 and indirectly6–7 several times in the past. In each case the answer was ‘No’ but in each case the answer was inconclusive. Doubts arose because of the observation that activation of T cells, in vivo, is an H–2-restricted event which appears unrestricted because of antigen processing by the host8–9. If antigen processing is involved in the induction of tolerance, then tolerance might also be an H–2-restricted process disguised to appear unrestricted. We report here a study designed to minimize antigen processing in which we find that T-cell tolerance induction to ‘self’ minor histocompatibility (H) antigens is indeed H–2-restricted.
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