Probing molecular interactions within class II MHC Aq/glycopeptide/T-cell receptor complexes associated with
Ida E Andersson1, Balik Dzhambazov, Rikard Holmdahl
1Department of Chemistry, Umeå University, SE-901 87 Umeå, Sweden.
Abstract:
T cells obtained in a mouse model for rheumatoid arthritis are activated by a glycopeptide fragment from rat type II collagen (CII) bound to the class II major histocompatibility complex Aq molecule. We report a comparative model of Aq in complex with the glycopeptide CII260-267. This model was used in a structure-based design approach where the amide bond between Ala261 and Gly262 in the glycopeptide was selected for replacement with psi[COCH2], psi[CH2NH2+], and psi[(E)-CH=CH] isosteres. Ala-Gly isostere building blocks were then synthesized and introduced in CII260-267 and CII259-273 glycopeptides. The modified glycopeptides were evaluated for binding to the Aq molecule, and the results were interpreted in view of the Aq/glycopeptide model. Moreover, recognition by a panel of T-cell hybridomas revealed high sensitivity for the backbone modifications. These studies contribute to the understanding of the interactions in the ternary Aq/glycopeptide/T-cell receptor complexes that activate T cells in autoimmune arthritis and suggest possibilities for new vaccination approaches.
More Related Videos
09:53Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
Published on: February 6, 2017
12:09Use of Single Chain MHC Technology to Investigate Co-agonism in Human CD8+ T Cell Activation
Published on: February 28, 2019
Related Concept Videos
Antigens Involved in Adaptive Immunity
Complete Antigens
Complete antigens possess both immunogenicity and reactivity.
T Cell Types and Functions
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Fibril-associated Collagen
For example, the type II collagen fibrils in cartilage have covalently bound type IX fibril-associated collagens at regular intervals. Other types of fibril-associated collagens are...
Antigen Processing Pathways
MHC Class I: Presenting Endogenous...
T Cell Activation and Clonal Selection
Naive T cells that have not yet encountered an antigen express two primary CD...
