In HLA-matched stem cell transplantation (SCT), Minor Histocompatibility Antigens (mHags) play major roles in the development of the GvT effect, but they are also responsible for the development of GvHD. mHags are polymorphic peptides presented by HLA molecules. They are derived from intracellular proteins encoded by allelic genes. While several mHags are expressed ubiquitously, mHags can also be derived from hematopoietic system specific proteins. Such hematopoietic-mHags are attractive targets to induce GvT without increasing the risk of GvHD. Therefore, a primary goal of our studies is to identify novel GvT associated hematopoietic-mHags. To this end we employ two different strategies:
a) Direct immunology (T cells to antigen): Recently we developed a novel and a powerful genetic method to precisely identify the genetic locus of mHags recognized by T cell clones. Using this method we identified the first hematopoietic mHag on the CD19 molecule which is presented to HLA class II restricted, CD4+ cytotoxic T cells (J.Exp.Med. 2008). The program needed for this strategy is a modified ssSNPer (originally by Dr. D. Nyholt). We made this program available for download from sourceforge (
http://sourceforge.net/projects/sssnper-to-mhag/). It can be used by everyone to identify novel mHags. Please refer to our paper (R. Spaapen et al; J.Exp.Med.; 2008) when reporting results obtained using this program.
b) Reverse immunology (polymorphic genes to T cells). We developed a novel and fully automated mHag prediction software to predict clinically relevant mHags on polymorphic genes. Using this program we have until now screened > 800 hematopoietic genes for the presence of putative mHags We are currently investigating the immunogenicity of 4 putative mHags encoded by SIGLEC5, SIPA1, CD33 and HCLS1.