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PMID: 11148223 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The immunogenicity of a new human minor histocompatibility antigen results from differential antigen processing.

The Journal of experimental medicine ·Vol. 193 ·No. 2 ·2001-01-15 ·Pages 195-206

Brickner AG, Warren EH, Caldwell JA, Akatsuka Y, Golovina TN, Zarling AL, Shabanowitz J, Eisenlohr LC, Hunt DF, Engelhard VH, Riddell SR

Abstract

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.

MeSH Terms
Alleles Amino Acid Sequence Antigen Presentation Base Sequence Clone Cells DNA Primers/genetics Epitopes/chemistry,genetics Female Humans Male Mass Spectrometry Minor Histocompatibility Antigens/chemistry,genetics,metabolism Molecular Sequence Data Pedigree Polymorphism, Genetic Reverse Transcriptase Polymerase Chain Reaction Sequence Homology, Amino Acid
Chemicals
DNA Primers Epitopes Minor Histocompatibility Antigens
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Brickner A G
Department of Microbiology, Beirne B. Carter Center for Immunology Research, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Warren E H
Caldwell J A
Akatsuka Y
Golovina T N
Zarling A L
Shabanowitz J
Eisenlohr L C
Hunt D F
Engelhard V H
Riddell S R
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.193.2.195
Published
2001-01-15
Pages
195-206
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2193344
Subset
IM
Grants
NIAID NIH HHS · AI39501 · United States
NIAID NIH HHS · AI33993 · United States
NIAID NIH HHS · AI20963 · United States
External Links
PubMed source DOI: 10.1084/jem.193.2.195 PMC Full Text View journal details
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