Molecular analysis of HLA class I and class II antigen loss mutants reveals a homozygous deletion of the DR, DQ, and part of the DP region: Implications for class II gene order
1986; Elsevier BV; Volume: 16; Issue: 2 Linguagem: Inglês
10.1016/0198-8859(86)90049-2
ISSN1879-1166
AutoresM Kellis, J.S. Lee, Jean W. Petersen, T.L. Bugawan, R DeMars,
Tópico(s)Immunotherapy and Immune Responses
ResumoThe mutant human B-lymphoblastoid cell lines, 721.174 and 721.180, previously reported to exhibit greatly reduced expression of human HLA class I and II antigens (DeMars et al., Hum Immunol 11:77, 1984), were analyzed by Southern blotting using class II cDNA and genomic clones as hybridization probes. All genomic sequences complementary to DRα, DRß, DQα, and DQß probes were absent from these mutants. DZα genomic sequences were deleted as were the DPα1 and DPß2 loci but the DPß2 and most, if not all, of the DPα2 locus were retained. However, no RNA transcripts for either DPα2 or DPß2 could be detected. The mapping of the deletion breakpoint within the DP cluster allows the orientation of the loci in the DP region with respect to the centromere as follows: centromere, DPß2, DPα2, DPß1, DPα1, (DQ, DR). In addition, the analysis of a set of DR−, DQ−, DP+ homozygous deletion mutants (721.82, 721.84, and 721.101) reveals a deletion breakpoint between the DQα1/DQß1 loci and the DQα2/DQß2 loci. These mutants retain DZα genomic sequences, tentatively mapping the DZα locus between the DQ and the DP region. The residual ability of the DR−, DQ−, DP− mutants (174 and 180) to stimulate allogeneic and autologous lymphoproliferative responses must be attributed to expression of as yet unidentified class II antigens, or to non-class II antigens.
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