Recessive T cell response to poly (Glu⁵⁰Tyr⁵⁰) possibly caused by self tolerance

The proliferative T cell response of inbred mouse strains to the random copolymer poly(Glu⁵⁰Tyr⁵⁰) (GT) was found to fall into two categories. Some strains responded only marginally (Δ cpm values < 10,000 and stimulation indices < 3), whereas other strains mounted a substantial response (Δ cpm 10,000 to 80,000, SI 3 to 30). The response is controlled by the A(α) and A(β) loci of the major histocompatibility complex (MHC), as well as by genes not linked to the MHC. Because the response is selectively inhibited by monoclonal antibodies specific for the A(α)A(β) molecule, we assume that its control by A loci is manifested as an A-restriction of the participating T (Ly-1(high), Ly-2^-) cells. It is of interest that the responsiveness is recessive in F₁ hybrids of responder and nonresponder strains that are H-2-identical, but differ at their genetic background. Nonresponsiveness of these F₁ mice is caused neither by a defect of antigen presentation, nor the result of immune suppression on priming or at the effector phase of the response. It is most likely the consequence of clonal deletion during the establishment of self-tolerance.