Using BALB/c and CBA/J mice, the Iregion associated (Ta) binding capacity and T-cell immunogenicity of a panel of 14 overlapping peptides that span the entire sequence of the protein staphylococcal nuclease (Nase) was examined to evaluate major histocompatibility gene complex (MHC) control of T-cell responses. Ta binding and Ia-restricted T-cell immunogenicity could be determined for a total of 54 peptide-MHC combinations. Only 30% of the 54 instances examined involved detectable la binding, but they represented almost all (12 of 13) of the immune responses found. However, binding to Ia was not sufficient to ensure T-cell immunogenicity, since only 70% of the binding events were productive-i.e., were associated with an immune response. Thus, Ta molecules have the expected characteristics of a highly permissive capacity for antigen interaction that allows them to function as restriction elements for a large universe of antigens. On the other hand, since the Ta molecules cannot distinguish between self and non-self, not all antigen-Ta interactions would be permitted to elicit a T-cell response. It appears that both Ta

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