Browse by author
Lookup NU author(s): David Scott, Dr Ingrid Ehrmann
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Minor histocompatibility Ags derive from self-proteins and provoke allograft rejection and graft-vs-host disease in MHC-matched donor-recipient combinations. In this study, we define the HYDk epitope of the HY minor histocompatibility Ag as the 8mer peptide RRLRKTLL derived from the Smcy gene. Using HY tetramers, the response to this peptide was found to be immunodominant among the four characterized MHC class I-restricted HY epitopes (HYDkSmcy (defined here), HYKkSmcy, HYDbUty, and HYDbSmcy). Indirect presentation stimulated a robust primary HYDkSmcy response. Indirect presentation and priming of HY-specific CD8+ T cells is also operative in the presence of a full MHC mismatch. To determine whether the indirect route of Ag presentation is required for HY priming, female parent into F1 (H2bxk) female recipient bone marrow chimeras were immunized with male cells of the other parental haplotype, limiting presentation to the direct pathway. The dominant H2b HY response (HYDbUty) was dependent on indirect presentation. However, the dominant H2k HY response (HYD kSmcy) could be stimulated efficiently by the direct pathway. In contrast, secondary expansion of both HYDkSmcy and HYD bUty-specific CD8+ T cells was effective only when Ag was presented by the direct route. Transgenic overproduction of Smcy mRNA within the immunizing cells resulted in a corresponding increase in the HYD kSmcy, HYDbSmcy, and HYKkSmcy-specific CD8 + T cell responses when presented via the direct pathway but did not enhance indirect presentation demonstrating the independent regulation of MHC class I-peptide occupancy in the two Ag-processing pathways. Copyright © 2005 by The American Association of Immunologists, Inc.
Author(s): Millrain M, Scott D, Addey C, Dewchand H, Ellis P, Ehrmann I, Mitchell M, Burgoyne P, Simpson E, Dyson J
Publication type: Article
Publication status: Published
Journal: Journal of Immunology
Year: 2005
Volume: 175
Issue: 11
Pages: 7209-7217
ISSN (print): 0022-1767
ISSN (electronic): 1550-6606
Publisher: American Association of Immunologists
PubMed id: 16301625