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Identification of the immunodominant HY H2-Dk epitope and evaluation of the role of direct and indirect antigen presentation in HY responses

Lookup NU author(s): David Scott, Dr Ingrid Ehrmann


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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.

Publication metadata

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