Antigen receptors on Thy-1+ CD3- CS-initiating cell. In vitro desensitization with hapten-amino acid or hapten-Ficoll conjugates, versus hapten-protein conjugates, suggests different antigen receptors on the immune cells that mediate the early and late components of murine contact sensitivity.

Abstract

In murine contact sensitivity (CS) models, cutaneous immune responses are caused by the activity of two different Ag-specific Thy-1+ CD5+ cells. These two different cell subsets act in an obligate sequence to mediate separate early and late components of CS that are accompanied respectively by skin swelling responses at 2 and 24 h after local challenge with the hapten. The early-acting CS-initiating cells are not conventional T cells inasmuch as they are surface negative for CD4, CD8, and CD3. In contrast to this non-MHC-restricted, CS-initiating cell, the classical late-acting CS effector T cell that is recruited locally is CD3+, CD4+, CD8-, and is MHC-restricted. In our study, we have conducted experiments in which a mixture of immune CS-initiating and CS-effector cells were desensitized by incubation in vitro at 37 degrees C with various hapten-amino acid and hapten-carrier conjugates, before i.v. transfer and subsequent ear challenge of normal recipient mice. Desensitization was achieved with multivalent complexes of the relevant hapten conjugated to a variety of unrelated nonmurine carrier proteins, and, in some instances, with monovalent hapten conjugated to amino acid. Because the CS-mediating cells were desensitized in a hapten-specific manner, but these same cells transferred CS reactivity that was hapten/MHC-class II specific, it was suggested previously that these results argued in favor of a two-receptor model for T cell recognition of Ag, one receptor for hapten and the other for MHC. Our study suggests that these findings need to be reinterpreted because CS reactions are mediated by two different, Thy-1+ Ag-specific cells that act in an obligate sequence. Our data suggest that the late-acting Ag/MHC-specific CS-effector T cells are not hapten-specific. In fact, desensitization with hapten alone has a locus of action solely on the Ag receptor of the first-acting Thy-1+ CS-initiating cells--which are therefore truly hapten-specific and which are required for local recruitment of the Ag/MHC-specific late CS-effector T cells.