Even though most eucaryotic proteins are glycosylated, very little is known on if, or how, the glycansinfluence essential immunological events such as antigen processing, major histocompatibility complex (MHC)restricted presentation, and recognition by T cells. We have used synthetic glycopeptides to elucidate thespecificity of T cell hybridomas, obtained by immunization with the glycoprotein type II collagen in a mousemodel for rheumatoid arthritis. To enable these studies, glycosylated and suitably protected derivatives of(
5R)-5-hydroxy-
L-lysine, and the similar 5-hydroxy-
L-norvaline, were prepared and then used in Fmoc solid-phase synthesis of glycopeptides related to the immunodominant fragment from type II collagen, CII(256-270). Evaluation of the synthetic glycopeptides provided evidence that antigen-presenting cells can indeedprocess glycoproteins to glycopeptides, which elicit a T cell response when presented by class II MHC molecules.A glycopeptide carrying a single
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D-galactosyl residue attached to hydroxylysine at position 264 in the centerof the CII(256-270) peptide was recognized by most of the hybridomas in a way involving specific contactsbetween the carbohydrate and the T cell receptor. The results suggest an explanation for the recent observationthat glycosylated type II collagen induces more severe forms of arthritis in the mouse than deglycosylatedtype II collagen and provide additional knowledge on how rheumatoid arthritis may occur also in humans.