K. Itakura

Evidence for two B-cell alloantigen loci in theHLA-D Region

Antigenic determinants recognizable by human antisera (Hon 7 and 2075abs sera) were found in a partially purified antigen preparation obtained from an HLA-D and -DR homozygous cell line (EBV-Wa). Sequential coprecipition tests showed that two determinants detectable with Hon 7 and 2075abs sera (Hon 7 and 2075abs determinants) were present on different molecules. These two antigenic determinants were shown to be allotypic and were expressed predominantly in the B-cell-rich fraction. Family studies showed that both antigenic determinants segregated concordantly with respectiveHLA haplotypes. In the population study, the 2075abs and Hon 7 determinants were shown to be in strong linkage disequilibrium and the 2075abs determinant perfectly correlated with the HLA-DRw4 specificity. The results indicate that the Hon 7 determinant is coded for by a gene distinct from alleles at theHLA-DR locus. Furthermore, the locus (Hon 7) coding for the Hon 7 determinant is suggested to be very closely linked with theHLA-DR locus.

Location of Lyb-2 on mouse chromosome 4

TheLyb-2 locus responsible for the B-lymphocyte alloantigen system Lyb-2 is located on chromosome 4 at a distance of 20.6±4.9 map units fromPgm-2. A three-point cross indicated the orderLyb-2: Mup-1∶b∶ Pgm-2.

Inheritance of asthma in families and its linkage to HLA haplotypes.

Four families in which asthma occurred in more than three members, and in which there were at least three children, were studied in terms of clinical symptoms, serum IgE levels determined by RIST and RAST, and HLA haplotypes. No association between clinical asthma and serum IgE level was found, but a close association between asthma and a particular HLA haplotype in a family was demonstrated. It was therefore postulated that a disease susceptibility gene closely linked to an HLA gene complex may play a role in the development of asthma.

Structure of the HLA-D Region

The major histocompatibility region of man (HLA) codes for two groups of polymorphic cell surface membrane antigens (4). One group comprises the products of the A, B, and C loci. The second group represents the human analogues of the mouse Ia antigens, which are coded by a series of alleles in the HLA-D region. The HLA-D locus was originally defined as a locus whose alleles code for HLA-D antigens defined by the mixed lymphocyte culture (MLC) test (5). The discovery of the I region gene products by the serological method in the mouse was a great stimulus for HLA-ologists, and the study of the human homologues of the murine Ia antigens, i.e. HLA-linked B cell alloantigens detected serologically, has attracted many investigators in the field of HLA and has been one of the most important topics in this field for the last four years (1). HLA-DR antigens. In the 7th international histocompatibility workshop held in Oxford in 1977, 180 antisera, which had been shown locally or in regional workshops to react with B lymphocytes or with chronic lymphatic leukemia (CLL) cells or B cell lymphoid lines, were selected from those submitted from all over the world. These typing sera were distributed to the participating laboratories, where the experiments were carried out. The data were collected by the organizers of each region, on punched cards in the standard format, and sent on magnetic tape to Oxford, where they were analyzed on Oxford Universitys computer (3). In the workshop, seven antigen specificities (DRw 1—DRw7), predominantly expressed on B lymphocytes and supposed to be coded by a series of alleles of one locus (HLA-DR), were established. These HLA-DR antigen specificities defined serologically showed a high correlation with HLA-D antigen specificities assigned on the basis of the MLC test (1) (Table 1). Thus DRw 1 is correlated with Dw1, DRw2 with Dw2, and so on. A good Hardy-Weinberg fit was observed for these seven specificities in the population study, suggesting that a set of these specificities is coded for by allelic genes at the same locus. In further consideration of the problem of cross-reaction between the DRw antigens, only one locus (HLA-DR) was proposed to elucidate the genetic structure of the HLA-linked B cell alloantigen system (3). In the Oxford workshop a cluster of antisera was noticed which reacted with both DRw4 and DRw7 antigens. One representative serum in this group, serum P3796, reacted almost exclusively with cells that have either DRw4 or DRw7 antigen. Bodmer et al used this serum in an absorption experiment (4). After absorption with