DIFFERENTIAL ACTIVATION OF MOUSE HEPATITIS VIRUS-SPECIFIC CD4(-CELLS IS DEFINED BY PEPTIDE LENGTH() CYTOTOXIC T)

In this study we have characterized the core epitope recognized by the MHV-A59-specific CD4(+) cytotoxic T lymphocyte (CTL) clones HS1 and B 6.1, derived from BALB/c and C57/BL6 mice, respectively. These CD4(+) clones respond to the promiscuous peptide fragment S-329-343 of the gl ycoprotein S of MHV-A59. The results indicate that the core peptides o f both clones overlap but are not identical. The core region of the HS 1 clone is an 8-mer, and comprises the amino acid residues S-332-339, whereas the minimal epitope for clone B6.1 is a 9-mer and comprises th e amino acid residues S-334-342. The peptide fragment S-329-343 activa tes all T-cell effector functions, including proliferation, cytokine s ecretion and cytolysis. However, in the present study we show that T-c ell activation is not an all-or-none phenomenon, in which T-cell stimu lation leads to activation of all T-cell effector functions. It appear s that changes in the length of a peptide ligand can differentially ac tivate the cytolytic machinery from proliferation and cytokine secreti on. Furthermore, the results indicate that, in our case, modulation of the flanking residues of the core epitopes did not convert the cytoki ne profile of polarized T-helper type-1 (Th1) clones into a Th2-type p attern.