Search

Ten novel HLA-DRB1 and one DRB3 alleles are described. Eight of the variants are single-nucleotide substitutions, four resulting in an amino acid change (DRB1*1145, *1148, *0828 and *1514) and four with silent substitutions (DRB1*040504, *130103, *160502 and DRB1*1447 and *1361) amino acid and one allele alters three nucleotides and two amino acids., ISSN-0001-2815 Pub. in Tissue Antigens, v66, p327-329, 2005.

The KIR2DL4 gene including a portion of exon 1 through exon 9 was sequenced from two families and eight cell lines from the International Histocompatibility Workshop (IHWS). Two known alleles and eight variants were detected. Overall, there were five synonymous and three nonsynonymous changes when the variants were compared to the coding sequences of the most closely related known alleles plus a common frameshift change in five of the variant alleles. Alignment of the new variants with all known alleles showed that the regions encoding the extracellular region and the cytoplasmic tail were the most polymorphic. Two non-synonymous changes, P146H and L161V, occurred in an extracellular immunoglobulin-like domain. Five of the eight variants had a single adenine deletion in the exon encoding the transmembrane region, potentially resulting in a truncated protein lacking the cytoplasmic tail. The distribution of the deletion variant among many KIR2DL4 alleles may explain the high frequency of this variation in the population. Four of the eight consanguineous IHWS cell lines were found to be heterozygous for KIR2DL4 carrying two alleles that differed from one another by a few nucleotide substitutions. Analysis of intron sequences in the families revealed the nature and distribution of interspersed repeat elements which comprise 46% of the KIR2DL4 nucleotide sequence and consist of 12 elements including six SINEs (13.73% of the total length), one LINE (12.41%), and five LTR elements (19.51%). The results revealed the presence of extensive diversity in the KIR2DL4 gene. This is the first extensive report providing both exon and intron data in related individuals., Pub. in Tissue Antigens, v65, p402-418, 2005.

In order for bone marrow transplantation to be an effective and successful therapeutic measure in the treatment of irradiation casualties, the donor marrow cells and the recipient must be matched for HLA antigens. Matching for antigens encoded by HLA-D appears to be most critical, however, we are just beginning to comprehend the complexity and importance of the HLA-D region. This contract was established to systematically analyze those HLA-D antigens most important for bone marrow transplantation and to develop and implement methods for matching large numbers of unrelated individuals for clinical bone marrow transplantation. We describe herein our progress in using cellular methods for elucidating the genetics of the HLA-D region and the initiation of biochemical approaches to clinical transplant matching. These methods include primed lymphocyte typing (PLT) generation of human T-lymphocyte clones (TLC's) that recognize histocompatibility antigens, homozygous typing cells (HTC) characterization and peptide map characterization. During the upcoming contract period, we will continue our efforts in cellular immunology, and will also continue to develop parallel programs in the immunochemistry of human alloantigens and serologic recognition of HLA antigens by human monoclonal antibodies.