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Evidence for major histocompatibility complex (MHC) restriction of soluble helper effects was observed in the generation of syngeneic killer T cells to trinitrophenyl-altered self. Ia-bearing T cells obscure the observation of such interactions, thus, must be removed to detect MHC restriction of nonspecific soluble helper factor supernates (HFS). Genetic mapping studies demonstrated that the strain producing HFS must be compatible in the H-21A region with the strain utilizing the helper molecules for optimal helper signals to be delivered.

Major histocompatibility complex restriction of soluble helper molecules in T cell responses to altered self.