We proposed to seek cancer susceptibility genes within the major histocompatibility locus on chromosome 6 in patients with various types of cancer and in high-risk cancer families. In order to accomplish this, we proposed to further develop a method of HLA-D typing which utilizes lymphoblastoid cell lines (LCL) instead of peripheral blood lymphocytes from donors who are homozygous at the HLA-D locus. Within the past year, we have further developed this technology and the computer software and interfacing it entails. We also compared this method of HLA-D typing with other methods and found good agreement. When the various alleles at the HLA-D locus were compared as they were represented by our LCL cell panel, it was possible to appreciate that alleles Dwl and 3 split and overlap in a pattern suggesting new allelic groups: 1a-3, 1b-3 and "true 3." The often-questioned allelic group, Dw8, was included within our group 1b-3. HLA typing by serological methods was established in our laboratories as a result of this award and will continue on a cost-effective basis after the award has expired. In addition, a screening program for new HLA antisera was established. The extensive LCL cell panel created for these studies now represents a unique research tool and has recently been utilized in several new ways: 1) to demonstrate that antisera to HLA-DR specifically inhibit growth of such cell lines, 2) to characterize the relationship between the two closely related loci of HLA-D and HLA-DR. During this year, we have critically reevaluated each LCL in our homozygous typing cell panel, deleted many, and added 17 new ones. All new entries to this cell panel will be from consanguineous donors. We have initiated the final phases of the project by contacting various cancer agencies to inform them about our capabilities and interest in typing high-risk cancer families. Several such families have already been typed; however, it is premature to state results.