chapter  14
10 Pages

Donor selection in allogeneic bone marrow transplantation Andrea L Pay, Ann-Margaret Little, J Alejandro Madrigal

Bone marrow transplantation (BMT) between individuals is now a routine treatment for a variety of haematological diseases, including chronic myeloid leukaemia (CML). The main drawback of this therapeutic procedure, however, is rejection of either the host tissue by the graft, or of graft tissue by the host.1 The ensuing allogeneic response is stimulated by both major and minor genetic differences between the donor and the recipient, and is mediated by the human leukocyte antigens (HLA) encoded by the major histocompatibility complex (MHC). HLA molecules can be divided into two groups – class I and II – based on their expression and function. The primary function of HLA class I molecules is to present peptides generated from proteins produced within the cell to cytotoxic T cells that express the CD8 co-receptor. These peptides are predominantly either of self origin and will initiate no immune response, since T cells will be tolerant to them, or of viral origin and their presentation will initiate a T-cell response in order to eliminate the virus-infected cell. HLA class II molecules present peptides from exogenously produced proteins, which have been internal-

ized and broken down within the cell. These class II molecules interact with helper T cells expressing the CD4 co-receptor.