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Human allospecific TLCs generated against HLA antigens associated with DRl through DRw8
Authors:Sandra Rosen-Bronson  Armead H Johnson  Robert J Hartzman  David D Eckels
Institution:(1) Laboratory of Immunogenetics, NIAID, NIH, Bethesda, Maryland, USA;(2) Lombardi Cancer Center, Georgetown University School of Medicine, Washington, D. C., USA;(3) Transplantation and Immunology Branch, Naval Medical Research Institute, Bethesda, Maryland, USA;(4) Immunogenetics Research Section, The Blood Center of Southeastern Wisconsin, Milwaukee, Wisconsin, USA
Abstract:We have studied the complexity and fine specificity of the HLA-D region using a panel of T lymphocyte clones generated against alloantigens associated with HLA-DR1 through DRw8. After extensive testing in population studies, 89 clones were tested in proliferation assays with 14 families. Segregation patterns were analyzed for haplotype associations by calculating sequential lod scores to test the likelihood that genes encoding epitopes detected by TLCs were linked to HLA genes. Four general categories were identified: (1) clonal responses that segregated with the same HLA-D region haplotype in all informative pedigrees; (2) clonal responses that segregated with HLA in all pedigrees but not always with the same haplotype; (3) clonal responses that segregated with HLA in some families but failed to segregate in others or produced equivocal results; (4) clonal responses that did not segregate with HLA haplotypes.Abbreviations used in this paper cpm counts per minute - DNV double normalized value - EBV Epstein-Barr virus - FCS fetal calf serum - HLA human MHC - HTC homozygous typing cell - LCL lymphoblastoid cell line - MHC major histocompatibility complex - MLC mixed lymphocyte culture - mAb monoclonal antibody - PBL peripheral blood lymphocyte - PLT primed lymphocyte typing - T-max maximized T test analysis - TCGF T-cell growth factor - TLC T-lymphocyte clone
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