Glycopeptides bind MHC molecules and elicit specific T cell responses

C. V. Harding, J. Kihlberg, M. Elofsson, G. Magnusson, E. R. Unanue

Research output: Contribution to journalArticlepeer-review

110 Scopus citations

Abstract

Carbohydrates are T cell independent antigens because they do not bind to MHC molecules. However, glycopeptides might potentially bind to MHC molecules via their peptide component for presentation to T cells. We have conjugated the disaccharide galabiose [Galα(1-4)Galβ] to the amino terminus of a T cell peptide determinant from hen egg-white lysozyme [HEL(52-61)]. The resulting glycopeptide (Gal2-52-61) and a nonglycosylated analogue containing tyrosine and glutamic acid at the amino-terminus (YE-52-61) bound equally well to purified I-A(k). T cell hybridomas were produced after immunization with Gal2-52-61. Many of the T cell hybridomas were glycopeptide-specific and responded to Gal2-52-61 but not to nonglycosylated synthetic peptides or to HEL presented by APC, indicating that the carbohydrate moiety influenced T cell recognition. Recognition was lost with the amino terminal attachment of the disaccharide to a peptide six amino acids longer at the amino terminus than HEL(52-61). Recognition also was lost with peptides containing only a single galactosyl residue or with galabiose bound to a different I-A(k) binding peptide. T cells directed to Gal2-52-61 recognized glycopeptides having significant variation in the disaccharide structure, such as HEL(52-61) glycopeptides carrying lactose, cellobiose, or hepta-o-acetylated galabiose. Peptide residues were important features of the T cell epitope; Ala substitutions of two critical T cell contact residues of HEL(52-61) (Tyr53 and Leu56) abrogated T cell reactivity to the glycopeptides without affecting binding to I-A(k). In conclusion, we propose that these T cells recognize a peptide conformation specific to glycopeptide- I-A(k) complexes and that this recognition does not involve specific interaction between the carbohydrate moiety and the T cell receptor.

Original languageEnglish
Pages (from-to)2419-2425
Number of pages7
JournalJournal of Immunology
Volume151
Issue number5
StatePublished - Jan 1 1993

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