The HA-2 minor histocompatibility antigen is derived from a diallelic gene encoding a novel human class I myosin protein.
Human minor histocompatibility Ags (mHag) present significant barriers to successful bone marrow transplantation. However, the structure of human mHag and the basis for antigenic disparities are still largely unknown. Here we report the identification of the gene encoding the human mHag HA-2 as a previously unknown member of the class I myosin family, which we have designated MYO1G. The gene is located on the short arm of chromosome 7. Expression of this gene is limited to cells of hemopoietic origin, in keeping with the previously defined tissue expression of the HA-2 Ag. RT-PCR amplification of MYO1G from different individuals led to the identification of two genetic variants, designated MYO1G(V) and MYO1G(M). The former encodes the peptide sequence previously shown to be the HA-2 epitope (YIGEVLVSV), whereas the latter shows a single amino acid change in this peptide (YIGEVLVSM). This change has only a modest effect on peptide binding to the class I MHC-restricted element HLA-A*0201, and a minimal impact on recognition by T cells when added exogenously to target cells. Nonetheless, as detected using either T cells or mass spectrometry, this amino acid change results in a failure of the latter peptide to be presented at the surface of cells that express MYO1G(M) endogenously. These studies have thus identified a new mHag-encoding gene, and thereby provide additional information about both the genetic origins of human mHag as well as the underlying basis of an Ag-positive vs Ag-negative state.
Pierce
R A
RA
Department of Microbiology and Carter Immunology Center, University of Virginia, Charlottesville, VA 22908, USA.
Field
E D
ED
Mutis
T
T
Golovina
T N
TN
Von Kap-Herr
C
C
Wilke
M
M
Pool
J
J
Shabanowitz
J
J
Pettenati
M J
MJ
Eisenlohr
L C
LC
Hunt
D F
DF
Goulmy
E
E
Engelhard
V H
VH
D000483:Alleles; D019943:Amino Acid Substitution; D017951:Antigen Presentation; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D000939:Epitopes / Q000235:genetics; D005091:Exons / Q000235:genetics; D005583:Fourier Analysis; D005796:Genes; D014644:Genetic Variation; D015234:HLA-A Antigens / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000378:metabolism; D015778:Minor Histocompatibility Antigens / Q000235:genetics* / Q000276:immunology; D005810:Multigene Family; D022423:Myeloid Cells / Q000378:metabolism; D009218:Myosins / Q000235:genetics* / Q000276:immunology; D009363:Neoplasm Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology
D000939:Epitopes; C080145:HA-2 antigen; D015234:HLA-A Antigens; C440608:MYO1G protein, human; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D009218:Myosins