III . Low Responder Ant igen - present ing Cells Funct ion Effectively to Present Ant igen to Selected T Cell Clones Derived from ( High Responder × Low Responder ) F 1 Mice

The immune response to certain synthetic polypeptide antigens and native proteins has been shown to be controlled by immune response (Ir) genes, which reside in the murine major histoeompatibility complex (MHC) 1 (reviewed in 1). The expression of such Ir gene control has been localized to T cells, B cells, and/or antigen-presenting cells (2-4). Support for the concept of Ir gene expression in antigen-presenting cells depends largely upon the observations that T cells from (high responder × low responder)Fl animals recognize (respond to) antigen in the context of antigen presentation by high responder antigen-presenting cells. Such immune T cells are not stimulated by antigen presented by antigen-presenting cells of low responder strains (5-7). Based upon these observations, it has been suggested that phenotypic low responsiveness is due to the inability of low responder antigen-presenting cells to process or bind antigen in such a way that it can be effectively recognized by T cells. Alternatively, these results can be interpreted to suggest that there are "holes" in the T cell repertoire in low responder mice (8). This hypothesis is based on the concept that T lymphocytes recognize antigen in conjunction with I region gene products on the cell surface of antigen-presenting cells. The basic postulate is that the association between certain I region gene products and self antigens antigens mimics the association between the same I region product and certain foreign antigens, thus allowing natural tolerance to eliminate responsiveness to such foreign antigens. Long-term, soluble antigen-reactive, MHC-restricted, proliferating T cells have been shown to be useful tools for analysis of the precise structure of antigen-presenting determinants (9, 10). In this report, we describe our observations on selected T cell clones derived from (high responder × low responder)F1 [(H-2" × H-2b)F1] mice that were immunized with poly(Tyr,Glu)-poly-D,L,-Ala-poly-Lys [(T,G)-A--L], which recognized (T,G)-A--L in association with antigen-presenting cells from low responder (H-2 a) mice. These data suggest that there is no functional defect in the ability of low responder antigen-presenting cells to "associate" (T,G)-A--L in an immunogenic form with the I-A k region product.