IMMUNIZATION WITH GLYCOSYLATED K-B-BINDING PEPTIDES GENERATES CARBOHYDRATE-SPECIFIC, UNRESTRICTED CYTOTOXIC T-CELLS

Cytotoxic T cells (CTL) recognize target proteins as short peptides pr esented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T ce ll receptor (TCR) recognition of target proteins and non-protein struc tures. How such T cell responses are generated is presently unclear. W e generated carbohydrate (CHO)-specific. MHC-unrestrictcd CTL response s by coupling di- and trisaccharides to K-b- or D-b-binding peptides f or direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central positions on the c arrier peptide. With two of these glycopeptides, with galabiose (Gal a lpha 1-4Gal; Gal(2)) bound to a homocysteine (via an ethylene spacer a rm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-d erived peptide (RGYVYQGL binding to K-b). CTL were generated which pre ferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal, epitope in a glycolipid. B y fractionation of CTL. preliminary data indicate that glycopeptide-sp ecific K-b-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The result s demonstrate that hapten-specific unrestricted CTL responses can be g enerated with MHC class I-binding carrier peptides. Different models t hat might explain the generation of such responses are discussed.