The Role of Class II Molecules in Mls 1a Recognition by CD4+ T Cells Is Independent of the CD4 Molecule

The interpretation of previous antibody inhibition and cell depletion experiments was that major histocompatibility complex (MHC) class II molecules are involved in presentation of Mls molecules to T cell receptors. However, a possible conclusion of several subsequent studies was that T cell receptors may in fact recognize Mls molecules in a class II-unassociated manner. We considered that if this interpretation of the relevant data was correct, the earlier demonstrated role of MHC class II molecules on Mls 1a antigen presenting cells in the response of CD4+ T cells might be only to serve as a ligand for the CD4 molecule on the responder cells. To test the possibility that the inhibition of the anti-Mls 1a response by anti-class II antibodies solely reflected such a CD4 class II molecular interaction we derived CD4- variants of two independent T cell receptor Vβ6-expressing, Mls 1a-responsive T hybrid clones. Since preliminary experiments to screen for responsiveness revealed that the CD4- variants of both T hybrid clones retained responsiveness to Mls 1a and the variants of one that was also responsive to staphylococcal enterotoxin B retained that responsiveness we concluded that there is no qualitative dependency of the responses of Vβ6 T cells to these two superantigens on a CD4-mediated activity. More importantly, the responses of the CD4- variants of the two T hybrid clones to MIs 1a retain the same susceptibility to inhibition by antibodies to MHC class II molecules exhibited by the parental T hybrids. These results indicate that the blocking of responses of CD4+ T cells to Mls 1a by both anti-H-2A and anti-H-2E antibodies is not due only to disruption of interactions between CD4 and H-2A or H2E molecules. The data are thus consistent with the class II molecule-dependent models of Mls 1a presentation to the T cell receptor which are discussed in the light of recent findings on the biochemical nature of the Mls 1a molecule.