The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational ModificationsJournal of Immunology
AbstractMinor histocompatibility (H) Ag disparities result in graft-vs-host disease and chronic solid allograft rejection in MHC-identical donor-recipient combinations. Minor H Ags are self protein-derived peptides presented by MHC class I molecules. Most arise as a consequence of allelic variation in the bound peptide (p) that results in TCR recognizing the p/MHC as foreign. We used a combinational peptide screening approach to identify the immune dominant H2Kb-restricted epitope defining the mouse H4b minor H Ag. H4b is a consequence of a P3 threonine to isoleucine change in the MHC-bound peptide derived from epithelial membrane protein-3. This allelic variation also leads to phosphorylation of the H4b but not the H4a epitope. Further, ex vivo CD8+ T lymphocytes bind phosphorylated Ag tetramers with high efficiency. Although we document the above process in the minor H Ag system, posttranslational modifications made possible by subtle amino acid changes could also contribute to immunogenicity and immune dominance in tumor immunotherapeutic settings.
Citation InformationRajwardhan Yadav, Yoshitaka Yoshimura, Alina Boestenau, Gregory J. Christianson, et al.. "The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications" Journal of Immunology Vol. 170 Iss. 10 (2003) p. 5133 - 5142
Available at: http://works.bepress.com/rangaiah_shashidharamurthy/13/