The H4b Minor Histocompatibility Antigen Is Caused by a Combination of Genetically Determined and Posttranslational Modifications

Document Type

Article

Publication Date

2003

Abstract

Minor 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.

Publication Title

Journal of Immunology

Volume

170

Issue

10

First Page

5133

Last Page

5142

Comments

This article was published in Journal of Immunology, Volume 170, Issue 10, Pages 5133-5142.

The published version is available at http://dx.doi.org/10.4049/jimmunol.170.10.5133 .

Copyright © 2003 American Association of Immunologists.

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