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Response of Murine T Cells to the Synthetic Polypeptide Poly-Glu⁵⁰Tyr^{50 1}

Carol T. Cady^*, Michael Lahn^*, Michaelann Vollmer^*, Moriya Tsuji, Seong Jun Seo, Christopher L. Reardon^§, Rebecca L. O’Brien^* and Willi K. Born^2,*

^* Department of Immunology, National Jewish Medical and Research Center, Denver, CO 80206; Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10010; Department of Dermatology, Chung-Ang University Pil-dong, Chung-ku, Seoul, South Korea; and ^§ Department of Dermatology, University of Colorado Health Sciences Center, Denver, CO 80262

Random heterocopolymers of glutamic acid and tyrosine (pEY) evoke strong, genetically controlled immune responses in certain mouse strains. We found that pE⁵⁰Y⁵⁰ also stimulated polyclonal proliferation of normal , but not ß, T cells. Proliferation of T cells did not require prior immunization with this Ag nor the presence of ß T cells, but was enhanced by IL-2. The T cell response proceeded in the absence of accessory cells, MHC class II, ß₂-microglobulin, or TAP-1, suggesting that Ag presentation by MHC class I/II molecules and peptide processing are not required. Among normal splenocytes, as with T cell hybridomas, the response was strongest with V1⁺ T cells, and in comparison with related polypeptides, pE⁵⁰Y⁵⁰ provided the strongest stimulus for these cells. TCR gene transfer into a TCR-deficient ß T cell showed that besides the TCR, no other components unique to T cells are needed. Furthermore, interactions between only the T cells and pE⁵⁰Y⁵⁰ were sufficient to bring about the response. Thus, pE⁵⁰Y⁵⁰ elicited a response distinct from those of T cells to processed/presented peptides or superantigens, consistent with a mechanism of Ig-like ligand recognition of T cells. Direct stimulation by ligands resembling pE⁵⁰Y⁵⁰ may thus selectively evoke contributions of T cells to the host response.

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