We have evaluated the ability of a peptide-specific, I-Ak-restricted murine T hybridoma to bind its Ag in the presence and absence of class II MHC molecules. The restricting Ia molecule, when supplied as a plasma membrane preparation of I-Ak-expressing APC, specifically increases the avidity of the Ag-binding complex by lengthening its t1/2, without affecting the rate at which the complex is formed. Experiments using mutated I-Ak molecules indicate that the ability of a mutant Ia species to

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... ent Ag is distinct from its ability to stabilize the Ag-recognition complex, suggesting that T cell stimulation depends not only upon stabilization of Ag-TCR-Ia complexes, but also upon distinct Ia-influenced conformational signals.