Minor Histocompatibility Antigen Typing by DNA Sequencing for Clinical Practice in Hematopoietic Stem-Cell Transplantation

In HLA-matched stem-cell transplantation (SCT), minor H antigens are key molecules driving allo-immune responses in both graft-versus-host disease (GvHD) and in graft-versus-leukemia (GvL) reactivity. Dissection of the dual function of minor H antigens became evident through their different modes of tissue and cell expression, i.e., hematopoietic system restricted or broad. Broadly expressed minor H antigens are the targets of immune responses in both arms of graft-versus-host (GvH) responses, i.e., both GvHD and GvL, whereas the immune responses against the hematopoietic system-specific minor H antigens are restricted to the GvL arm of SCT. Evidently, it is this latter group of minor H antigens that can function as curative tools for stem-cell (SC)-based immunotherapy of hematological malignancies and disorders. The HLA-matched patient/donor combinations, incompatible for one of the hematopoietic-specific minor H antigens, are suitable for minor H antigen immunotherapy (Goulmy, Immunol Rev 157:125–140, 1997). Information on the minor H antigen phenotype is therefore needed. Hereto, genomic typing for minor H antigens has been implemented in many HLA laboratories. Here, we firstly summarize the relevance of minor H antigens particularly in hematopoietic SCT. Secondly, we describe a method for typing the various polymorphic minor H antigens molecularly identified to date by DNA sequencing.