HLA-D typing with lymphoblastoid cell lines. VI. Rationale and goals of data reduction

This report documents various characteristics of HLA-D typing by mixed leukocyte culture reactions when lymphoblastoid cell lines (LCLs) are substituted for peripheral blood lymphocytes as the stimulator cells. It also provides the rationale for designing the computer program described in the subsequent report. In such experiments, each donor to be HLA-D typed is stimulated with a panel of 30-50 HLA-D homozygous LCLs, each defined HLA-D allele being represented by several different human homogygous typing cells (LCT-HTCs). Variability in the strength of eahc donor's general response and in the strength of stimulation by each LCL-HTC makes it necessary to normalize raw data before the responses of various combinations can be compared and typing responses distinguished from non-typing responses. The autologous response and its equivalent effect among allogenetic combinations, the so-called "autologous-stimulation" effect, must also be distinguished from true allogeneic responses. The latter has been accomplished by "modelling," as described in the subsequent report. EBV-negative donors can also be HLA-D typed by this method despite the EBV-positivity of the LCL-HTCs. Preliminary analyses suggest that the HLA-D alleles defined by this method appear to segregate with appropriate haplotypes in family studies.