6.833333
#13
MEASURING HISTOCOMPATIBILITY IN ALLOGENEIC BONE MARROW TRANSPLANTATION.
Pedro Cano M.D. 1 and Marcelo Fernandez-Vina 1. 1 Laboratory Medicine, M.D. Anderson Cancer Center, Houston, TX, USA .
This is a study on the measurement of histocompatibility between two subjects. Both host-versus-graft (HvG) and graft-versus-host (GvH) immune directions must be considered (I). Each HLA locus must be evaluated separately (L). A different measurement must be made for each HLA molecule in each locus in the immune target (the graft in HvG and the host in GvH); that will typically be two per locus, and one in homozygous cases, but it can be one, two or four in the case of DQ heterodimers (X). Which DQA1 alleles combine with which DQB1 alleles must be taken into account. It is postulated that the number of copies of an HLA molecule on the cell membrane are important in eliciting an immune response, and that the density of molecules is diluted with the number of combinations of DQA1 and DQB1 heterodimers (N). Histocompatibility is measured based on the distance in a vector space where HLA molecules are represented as vectors, and where the coordinates are the sequence variables of these molecules (D). Each coordinate, representing an amino acid position, has a scale or weight depending on how critical that position is in the presentation of peptides and the recognition by T cells. A putative distance matrix of allele distance based on an assigned weight system for each position is presented. In addition, KIR-ligand matching must be considered for each of the main KIR receptors. As the role of HLA antibodies in BMT is evaluated an antibody match must be included too. Histocompatibility is defined as the relation R(I, L, X, N, D) between the variables mentioned above, and evaluated in reference to a donor and a recipient. This relation sets the foundation to select optimal donors in the absence of a perfect HLA match.