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Immunosuppressive Factor(s) Specific for L-Glutamic Acid⁵⁰-L-Tyrosine⁵⁰ (GT)

I. Production, Characterization, and Lack of H-2 Restriction for Activity in Recipient Strain¹

Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115

Abstract

The random synthetic copolymer of L-glutamic acid⁵⁰-L-tyrosine⁵⁰ (GT) fails to elicit a GT-specific antibody response in all inbred strains of mice tested. Preimmunization with GT specifically inhibits a GT-MBSA response in certain, H-2^d,k,s, but not other, H-2^a,b,q, nonresponder mice. This unresponsiveness is mediated by GT-specific suppressor T cells. Extracts prepared from lymphoid cells of GT-primed suppressor haplotype mice inhibit the development of primary GT-specific antibody responses to GT-MBSA in normal syngeneic mice. Nonsuppressor haplotype mice do not produce GT-specific suppressor factor. The GT-suppressive extract has affinity for antigen and a m.w. of less than 50,000 daltons, thus, resembling antigen-specific immunosuppressive factors already described. However, the GT-suppressive extract does not appear to have H-2 restrictions since it works across allogeneic barriers. Evidence is presented that two genes are required for factor-mediated suppression.

Footnotes

¹ This work was supported by Grant AI-09920 from the National Institutes of Health.

² Supported by Grant CA-09130 from the United States Public Health Service.

³ Present Address: Department of Hematology, Pitie - Salpetriere, 91 Boulevard de L'Hopital, Paris, France.

⁴ On leave of absence from the Pasteur Institute, Paris, France; supported by a fellowship from the Cancer Research Institute, Inc.