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Original Article

^a Department of Microbiology, Beirne B. Carter Center for Immunology Research,
^b Department of Pathology, University of Virginia, Charlottesville, Virginia 22908
^c Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109
^d University of Washington, Seattle, Washington 98195
^e Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901
^f Department of Microbiology and Immunology and the Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107
Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, MR4 Bldg., Box 4012, Charlottesville, VA 22908.804-924-1221804-924-2423

vhe{at}virginia.edu

Minor histocompatibility antigens (mHAgs) present a significant impediment to organ and bone marrow transplantation between HLA-identical donor and recipient pairs. Here we report the identification of a new HLA-A*0201–restricted mHAg, HA-8. Designation of this mHAg as HA-8 is based on the nomenclature of Goulmy (Goulmy, E. 1996. Curr. Opin. Immunol. 8:75–81). This peptide, RTLDKVLEV, is derived from KIAA0020, a gene of unknown function located on chromosome 9. Polymorphic alleles of KIAA0020 encode the alternative sequences PTLDKVLEV and PTLDKVLEL. Genotypic analysis demonstrated that the HA-8–specific cytotoxic T lymphocyte (CTL) clone SKH-13 recognized only cells that expressed the allele encoding R at P1. However, when PTLDKVLEV was pulsed onto cells, or when a minigene encoding this sequence was used to artificially translocate this peptide into the endoplasmic reticulum, it was recognized by CTLs nearly as well as RTLDKVLEV. This indicates that the failure of CTLs to recognize cells expressing the PTLDKVLEV-encoding allele of KIAA0020 is due to a failure of this peptide to be appropriately proteolyzed or transported. Consistent with the latter possibility, PTLDKVLEV and its longer precursors were transported poorly compared with RTLDKVLEV by transporter associated with antigen processing (TAP). These studies identify a new human mHAg and provide the first evidence that minor histocompatibility differences can result from the altered processing of potential antigens rather than differences in interaction with the relevant major histocompatibility complex molecule or T cell receptor.

Key Words: minor histocompatibility antigens • antigen processing • graft versus host disease • transplantation • Fourier transform mass spectrometry

Abbreviations used in this paper: BMT, bone marrow transplantation; CAD, collision-activated dissociation; CEPH, Centre d'Étude du Polymorphisme Humain; ER, endoplasmic reticulum; ESI, electrospray ionization; FTMS, Fourier transform MS; HFBA, heptafluorobutyric acid; ID, inner diameter; mHAg, minor histocompatibility antigen; MS, mass spectrometer; RP, reverse phase; RT, reverse transcription; TAP, transporter associated with antigen processing.

© 2001 The Rockefeller University Press

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