Identification of the minimal glycopeptide core recognized by T cells in a model for rheumatoid arthritis

TY - JOUR

T1 - Identification of the minimal glycopeptide core recognized by T cells in a model for rheumatoid arthritis

AU - Holm, L

AU - Kjellen, P

AU - Holmdahl, Rikard

AU - Kihlberg, J

N1 - The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)

PY - 2005

Y1 - 2005

N2 - Collagen induced arthritis (CIA) is a common mouse model for rheumatoid arthritis. Two sets of truncated peptides derived from type II collagen have been prepared and tested for binding to A(q), a MHC-II molecule associated with development of CIA. Binding to A(q) correlated well with predictions from a computer-based model. T-cell hybridomas, obtained in CIA, were also used to study the ability of A(q) bound peptides to trigger a T-cell response. The minimal peptide epitope required for binding, as well as for giving a T-cell response, was determined to be CII260-267. In collagen this epitope is often glycosylated at hydroxylysine 264 and glycosylation has been shown to be an immunodominant feature in CIA. Synthesis and evaluation of CII260-267 carrying a beta-D-galactosyl moiety at position 264 revealed that this glycopeptide stimulated representative members from a panel of carbohydrate-specific T-cell hybridomas obtained in CIA.

AB - Collagen induced arthritis (CIA) is a common mouse model for rheumatoid arthritis. Two sets of truncated peptides derived from type II collagen have been prepared and tested for binding to A(q), a MHC-II molecule associated with development of CIA. Binding to A(q) correlated well with predictions from a computer-based model. T-cell hybridomas, obtained in CIA, were also used to study the ability of A(q) bound peptides to trigger a T-cell response. The minimal peptide epitope required for binding, as well as for giving a T-cell response, was determined to be CII260-267. In collagen this epitope is often glycosylated at hydroxylysine 264 and glycosylation has been shown to be an immunodominant feature in CIA. Synthesis and evaluation of CII260-267 carrying a beta-D-galactosyl moiety at position 264 revealed that this glycopeptide stimulated representative members from a panel of carbohydrate-specific T-cell hybridomas obtained in CIA.

KW - T cell

KW - glycopeptide

KW - collagen

KW - rheumatoid arthritis

U2 - 10.1016/j.bmc.2004.10.011

DO - 10.1016/j.bmc.2004.10.011

M3 - Article

VL - 13

SP - 473

EP - 482

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 2

ER -