HapMap scanning of novel human minor histocompatibility antigens.
Minor histocompatibility antigens (mHags) are molecular targets of allo-immunity associated with hematopoietic stem cell transplantation (HSCT) and involved in graft-versus-host disease, but they also have beneficial antitumor activity. mHags are typically defined by host SNPs that are not shared by the donor and are immunologically recognized by cytotoxic T cells isolated from post-HSCT patients. However, the number of molecularly identified mHags is still too small to allow prospective studies of their clinical importance in transplantation medicine, mostly due to the lack of an efficient method for isolation. Here we show that when combined with conventional immunologic assays, the large data set from the International HapMap Project can be directly used for genetic mapping of novel mHags. Based on the immunologically determined mHag status in HapMap panels, a target mHag locus can be uniquely mapped through whole genome association scanning taking advantage of the unprecedented resolution and power obtained with more than 3 000 000 markers. The feasibility of our approach could be supported by extensive simulations and further confirmed by actually isolating 2 novel mHags as well as 1 previously identified example. The HapMap data set represents an invaluable resource for investigating human variation, with obvious applications in genetic mapping of clinically relevant human traits.
Kamei
Michi
M
Aichi Cancer Center Research Institute, Nagoya, Japan.
Nannya
Yasuhito
Y
Torikai
Hiroki
H
Kawase
Takakazu
T
Taura
Kenjiro
K
Inamoto
Yoshihiro
Y
Takahashi
Taro
T
Yazaki
Makoto
M
Morishima
Satoko
S
Tsujimura
Kunio
K
Miyamura
Koichi
K
Ito
Tetsuya
T
Togari
Hajime
H
Riddell
Stanley R
SR
Kodera
Yoshihisa
Y
Morishima
Yasuo
Y
Takahashi
Toshitada
T
Kuzushima
Kiyotaka
K
Ogawa
Seishi
S
Akatsuka
Yoshiki
Y
D002874:Chromosome Mapping / Q000379:methods*; D018604:Epitope Mapping / Q000379:methods; D005819:Genetic Markers; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000235:genetics*; D009369:Neoplasms / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014181:Transplantation Immunology
D005819:Genetic Markers; D015778:Minor Histocompatibility Antigens