Neonatally tolerant mice fail to react against virus-infected tolerated cells

Abstract

IN mice, immune effector functions mediated by thymus-derived lymphocytes (T cells) are restricted by the major histocompatibility (H–2) gene complex (see ref. 1 for review). Thus, virus-stimulated cytotoxic T cells are specific for both viral antigen(s) and self-cell-surface structures coded in the K or D region of H–2 (refs 2, 3). Two general hypotheses have been proposed to explain H–2 restriction^2–5. First, T cells possess two independently, clonally expressed, but linked receptors, one for the foreign antigenic determinant and one for the relevant self-marker (dual receptor model); second, T cells have a single clonally distributed receptor for a complex of foreign antigen plus self or for virally altered self-markers (altered self model). To date no conclusive proof exists for one hypothesis or the other. The altered self model is the simpler concept of the two; on the other hand, the fact that cytolytic interactions against minor histocompatiblity antigens are H–2 restricted and that the idiotypic determinants of T cell-receptors are identical with those of immunoglobulins of the same specificity^6–8 are probably more compatible with a dual receptor.