Is self tolerance H–2 restricted?

Abstract

An individual's immune system must be capable of responding to a wide variety of antigens, but must not react against tissues of the individual itself. The specificity of this ‘self tolerance’ is determined early in life^1–3 and recent work has dealt with the mechanisms by which self tolerance is maintained^4,5. We report here a study designed to determine whether products of the major histocompatibility complex are involved in the induction of self tolerance; in particular, whether the induction of self tolerance in the mouse is H–2 restricted. H–2 restriction refers to the finding that mouse T cells generally recognize foreign antigens only when presented in association with the products of H–2 alleles^6–8. We questioned whether T-cell precursors are made tolerant directly by antigen alone, or whether the antigen must be associated in the cell membrane with an appropriate H–2 molecule. We find that T-cell tolerance to ‘self’ membrane components does not seem to be H–2 restricted and discuss the possibility that this apparent lack of H–2 restriction is due to antigen processing.