Amputation of a suppressor determinant on lysozyme reveals underlying T-cell reactivity to other determinants

Abstract

THE response to several thymus-dependent antigens is influenced by immune response (Ir) genes, usually those of the major histocompatibility complex. However, the relevant gene products and their cellular sites of action have not been fully characterised. It is evident that in certain cases, the Ir genes can function to select those determinants which will be presented to activate T cells. This control operates, at least in part, at the level of macrophage–T-cell interactions. We have previously proposed¹ that the failure of a T-cell response in H–2^b mice following immunisation with chicken lysozyme (HEL) could be due to preferential stimulation of suppressor T cells. A suppressor mechanism which nullifies the activity of lysozyme-specific T-helper cells has been reported from our laboratory². Comparison of the amino acid sequence of various closely related lysozymes reveals that molecules which have tyrosine at position 3 are immunogenic in H–2^b mice whereas lysozymes with phenylalanine at position 3 are non-immunogenic in such strains³. We have considered the possibility that the latter lysozymes possess a determinant that preferentially stimulates suppressor cells in H–2^b mice, whereas the former lack this ‘suppressor determinant’. Other studies^4–6, including those by Schwartz et al.⁷ and Turkin and E.E.S.⁸, support a phenomenon of generalised suppression caused by restricted determinants. Here, we demonstrate that a strain which is unresponsive to HEL and whose T-cell proliferative activity is absent following immunisation with the entire molecule, possesses the potential to generate a vigorous T-cell response directed against a large fragment of the antigen. Suppressor cells directed against a restricted determinant on the molecule obscure this competence to respond to the majority of the molecule.