Autoreactive T lymphocytes are clonally deleted during maturation in the thymus. Deletion of T cells expressing particular receptor V beta elements is controlled by poorly defined autosomal dominant genes. A gene has now been identified by expression of transgenes in mice which causes deletion of V beta 14+ T cells. The gene lies in the open reading frame of the long terminal repeat of the mouse mammary tumour virus.

The predominant class II, or Ia, antigen of the human major histocompatibility complex is HLA-DR. It consists of an a and a 13 chain, the latter being responsible for the remarkable polymorphism of these Ia antigens. Studies with cloned genes had shown the existence of more than one DR 13-chain locus. We have isolated about 100 kilobases of the HLA-DR 13-chain gene region from a cosmid library generated from a consanguineous homozygous B-cell line of the DR3 haplotype. Three HLA-DR 13-chain genes have been characterized. They are arranged in a head-to-tail orientation. One of the genes lacks the region encoding the first domain of the DR 13 chain. The two other genes are transcribed, as shown by RNA blot hybridization analysis. A striking restriction site homology has been found within the DR 13-chain gene cluster, suggesting a recent duplication event involving at least 25 kilobases of DNA. Moreover, the molecular map of DR 13 chain genes cloned from B-cell lines of two other HLA-DR haplotypes shows extensive homology between alleles of a given DR 1-chain locus.The class II antigens of the major histocompatibility complex are highly polymorphic transmembrane glycoproteins, consisting of an a subunit and a p subunit. These molecules are located predominantly on the surface of macrophages and B cells. They play a key role in the control of the immune response, functioning in cell-cell interactions and antigen presentation to regulatory T lymphocytes. In the human major histocompatibility complex (HLA), the class II molecules have been mapped to the HLA-D region on chromosome 6. Three subregions have been defined, DP, DQ, and DR. The HLA-DR antigen is the predominant surface product and it is the p chain that is responsible for the DR polymorphism (for reviews, see refs. 1 and 2).The molecular organization of the HLA-D region has not yet been elucidated. The restriction map of the DP subregion is known. There are two DP a-and p-chain loci (3) found as a-p pairs with the a and p chain genes in a head-to-head orientation (4-6). The organization of the DQ and DR subregions is not known, although the genetic complexity of these subregions has been documented. There are two DQ a loci (7,8) and two DQ p loci (9, 10). The HLA-DR subregion has been shown to contain only one nonpolymorphic a-chain gene (11,12). Analysis of cDNA clones (13, 14) and genomic clones (10), as well as direct studies of cellular DNA by Southern blot hybridization (15), has allowed us to establish the existence of multiple DR p-chain loci.In this study, we report the characterization of overlapping cosmid clones containing DR p-chain genes isolated from a genomic library prepared from DNA of a HLA-homozygous individual. Three DR p-chain genes in a head-to-tail conformation have been aligned. Two of these genes are transcribed, while the third one appears to be truncated, lacking the first domain. Extensive restriction site homology between DR P-chain genes within the same haplotype has been observed, suggesting a recent duplication event. ...

No abstract

No abstract

No abstract