Response of murine gamma delta T cells to the synthetic polypeptide Poly-Glu(50)Tyr(50)

Random heterocopolymers of glutamic acid and tyrosine (pEY) evoke strong, g enetically controlled immune responses in certain mouse strains. We found t hat pE(50)Y(50) also stimulated polyclonal proliferation of normal gamma de lta, but not alpha beta, T cells, Proliferation of gamma delta T cells did not require prior immunization with this Ag nor the presence of alpha beta T cells, but was enhanced by IL-2, The gamma delta T cell response proceede d in the absence of accessory cells, MHC class II, beta(2)-microglobulin, o r TAP-1, suggesting that Ag presentation by MHC class I/II molecules and pe ptide processing are not required. Among normal splenocytes, as with gamma delta T cell hybridomas, the response was strongest with V gamma 1(+) gamma delta T cells, and in comparison with related polypeptides, pE(50)Y(50) pr ovided the strongest stimulus for these cells. TCR gene transfer into a TCR -deficient alpha beta T cell showed that besides the TCR, no other componen ts unique to gamma delta T cells are needed. Furthermore, interactions betw een only the T cells and pE(50)Y(50) were sufficient to bring about the res ponse. Thus, pE(50)Y(50) elicited a response distinct from those of T cells to processed/presented peptides or superantigens, consistent with a mechan ism of Ig-like ligand recognition of gamma delta T cells, Direct stimulatio n by ligands resembling pE(50)Y(50) may thus selectively evoke contribution s of gamma delta T cells to the host response.