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L cells expressing DQ molecules of the DR3 and DR4 haplotypes: reactivity patterns with mAbs
Authors:Dimitri S Monos  Eszter Czanky  Santa J Ono  Susan F Radka  Dietmar Kappes  Jack L Strominger
Institution:(1) Department of Biochemistry and Molecular Biology, Harvard University, 02138 Cambridge, MA, USA;(2) Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, 19104 Philadelphia, PA, USA;(3) Regeneron Pharmaceuticals Inc., 10591 Tarrytown, NY, USA;(4) Fox Chase Cancer Center, 19111 Philadelphia, PA, USA;(5) Present address: Department of Pathology and Laboratory Medicine, 7 Founders Pavilion, University of Pennsylvania Medical Center, 3400 Spruce Street, 19104 Philadelphia, PA, USA;(6) Present address: Department of Medicine, Johns Hopkins Medical School, 21224 Baltimore, MD, USA
Abstract:cDNAs coding for the HLA class II DR and DQagr and beta chains of the diabetogenic haplotypes DR3 and DR4 were introduced into a mammalian expression vector and transfected into L-cell mouse fibroblasts to produce cells expressing individual human class II molecules. Stable L transfectants were generated expressing each of the DR or DQ isotypes of the cis-encoded agr and beta chains of the DR3 or DR4 haplotypes, as well as the trans-encoded agr and beta chains of the DQ molecules of the two haplotypes. However, isotype mismatched combinations (DRagr/DQbeta or DQagr/DRbeta) did not result in any stable transfectants. The stable DQ L-cell transfectants obtained, along with homozygous B-cell lines expressing the DQ2 and DQ8 specificities, were tested against a large panel of twentyone anti-HLA class II monoclonal antibodies (mAbs). Their unusual reactivity patterns are described including the failure of most ldquopan-DQrdquo mAbs to react with all DQ expressing L-cell transfectants. Interestingly, some mAbs react with certain agrbeta heterodimers expressed on B-LCL but fail to recognize the same heterodimers expressed on the transfectants. This is suggestive of minor structural modifications that class II molecules undergo depending on the cells they are expressed on.The nucleotide sequence data reported in this paper have been submitted to the GenBank nucleotide sequence database and have been assigned the accession number U07848. The name DQB1 * 0202 was officially assigned by the WHO Nomenclature Committee in April 1994. This follows the agreed policy that, subject to the conditions stated in the most recent Nomenclature Report (Bodmer et al. 1992), names will be assigned to new sequences as they are identified. Lists of such new names will be published in the following WHO Nomenclature Report
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