Insulin-dependent diabetes mellitus (IDDM) is associated with several DR3- or DR4-containing ancestral haplotypes (AHs). Using pulsed field gel electrophoresis (PFGE), long range maps of 35 haplotypes have been derived and classified. Two diabetogenic DR3-containing AHs (8.1 and 18.2) possess deletions in the central non-HLA region; these have not been found on non-diabetogenic AHs tested to date. In addition, 8.1 and 18.2 also carry other deletions not found on other AHs. Three DR4 containing AH lack a Not I site, which may imply excision of an unidentified gene. These and other data suggest that deletions may be relevant to the pathogenesis of autoimmune disease, possibly through causing quantitative differences in autoimmune responses involved in IDDM. The MHC contains several regions of potential interest in relation to susceptibility to IDDM; these may explain the association with only certain DR3- and DR4-carrying AH and DR3,4 heterozygosity in terms of cis and trans interactions. On the other hand, the class II region may be particularly important in protection.
SUMMARY Alloimmunization of BALB/c (H‐2 d ) female mice with allogeneic spleen cells from C57BL/6 (H‐2 b ) or CBA/H (H‐2 k ) mice protects BALB/c offspring from graft‐versus‐host disease (GVH‐D) following neonatal intraperitoneal inoculation of high doses of spleen cells respectively of C57BL/6 or CBA/H strains of mice. The mice survived GVH‐D over one year after the allogeneic inoculum 24–48 h after birth and they did not show any signs of GVH reaction nor splenomegaly. We show that this phenomenon is antibody mediated and affects the developing immune system of the foetus. Repeated immunization of virgin female BALB/c with allti‐H‐2 b or anti‐H‐2 k antisera (Abl) can equally abrogate GVH‐D in their newborn offspring challenged at 24–48 h after birth with allogeneic spleen cells of H‐2 b or H‐2 k phenotype. Our results demonstrate that protection from GVH‐D is not specific to the immunizing strain and occurs when the neonatal mice are challenged with C57BL/6 or CBA/H spleen cells. There is thus crossreactivity of tolerance against H‐2 specificities. In this study we also report on the in vitro cellular immune responses of the surviving GVH‐resistant mice and demonstrate that these responses against both the challenge and third party lymphocytes are impaired.
Available evidence suggests that there are at least 30 different proteins at the red cell surface. These proteins vary in abundance from a few hundred copies/cell to more than a million copies/cell. Recently, a new Glycophorin gene (Glycophorin E) has been identified and sequenced. In this paper evidence is presented that a monoclonal anti-M detects the product of the Glycophorin E gene in normal red cells.
International Journal of ImmunogeneticsVolume 17, Issue 4-5 p. 343-345 THE FUTURE OF MABS WORKSHOPS AND THE FUTURE OF BLOOD BANKS B. E. Samuelsson, Corresponding Author B. E. Samuelsson Department of Medical Biochemistry and Regional Blood Center, Sahlgren's Hospital, University of Göteborg, SwedenB.E. Samuelsson, Department of Medical Biochemistry, and Regional Blood Center, University of Goteborg, Sweden.Search for more papers by this authorL. Messeter, L. Messeter University Hospital Blood Center, Lund, SwedenSearch for more papers by this author B. E. Samuelsson, Corresponding Author B. E. Samuelsson Department of Medical Biochemistry and Regional Blood Center, Sahlgren's Hospital, University of Göteborg, SwedenB.E. Samuelsson, Department of Medical Biochemistry, and Regional Blood Center, University of Goteborg, Sweden.Search for more papers by this authorL. Messeter, L. Messeter University Hospital Blood Center, Lund, SwedenSearch for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1744-313X.1990.tb00886.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume17, Issue4-5August 1990Pages 343-345 RelatedInformation
SUMMARY The rabbit MHC class II DP, DQ, and DR alpha and beta chain genes were transfected into murine B lymphoma cells. The transfected cells expressed R‐DQ and R‐DR molecules on the cell surface but they did not express the R‐DP genes either on the cell surface or at the level of mRNA. Northern blot analyses showed that the R‐DP genes were expressed, albeit at low levels, in rabbit spleen. Similar analyses showed that the R‐DQ and R‐DR genes were expressed at high levels in rabbit spleen. A new monoclonal anti‐rabbit class II antibody, RDR34, has been developed and shown to react with the R‐DR transfected cells and not with the R‐DQ transfected cells. The previously described monoclonal anti‐rabbit class II antibody, 2C4, reacted with the R‐DQ transfected cells and not with the R‐DR transfected cells. Thus, 2C4 and RDR34 MAb's are specific for the R‐DQ and R‐DR molecules, respectively. Each of the antibodies reacted with approximately 50% of rabbit spleen cells as shown by immunofluorescent antibody studies.
SUMMARY A comparison of lymphocyte antigens showed that 32 of the 33 BoLA antigens defined at the third international BoLA workshop (Bull et al ., 1989) corresponded to previously defined local antigens (Stear et al ., 1988). The third workshop antigen w18 had no locally defined equivalent. All 32 antigens were shown in family studies to be expressed by autosomal co‐dominant genes, and all 32 workshop antigens were shown to be products of the BoLA system. After excluding the supertypic antigens, nearly all animals tested possessed only one or two antigens and there were no observed recombinants in family studies. These results do not exclude the possibility that the 32 workshop antigens are the products of one locus ( BoLA‐A ).
Forty-six numbered Rh antigens which are detected in serological tests are extant; antigens which were most recently numbered are of high or of low incidence. The identification of high incidence Rh antigens through studies involving cells with rare Rh phenotypes, including Rhnull cells, is described briefly. The serological investigations and family studies required to show that a low incidence antigen is an Rh antigen are illustrated by a description of the JAL (Rh48) antigen. Heterogeneity of polymorphic Rh antigens revealed by using monoclonal antibodies (MABS) is demonstrated by consideration of the Rh antigen D. A summary of results of serological tests shows that monoclonal anti-D antibodies define eight D epitopes. Partial D antigens of the D categories are reassessed in terms of expression of D epitopes.
HLA-A,B specificities were analysed on the neoplastic blasts of a panel of 69 lymphoblastic (ALL) and 50 non lymphoblastic (ANLL) acute leukaemias at onset using the standard lymphocytotoxicity technique. Analysis of the number of detected specificities per locus and, when possible, comparison of the results with those obtained on lymphocytes of the same patients during remission revealed many alterations in the expression of A,B specificities including extra specificities both at the HLA-A and -B loci mainly on lymphoblasts and missed specificities mainly at the HLA-B locus on myeloblasts. Lack of A,B antigens was complete in 6.2% of all tested samples (9% of ANLL) and selective for all the products of one locus in 16.8% of all tested samples (27.7% of ANLL). A decrease of class I molecules on the cell surface was evidenced with MoAb W6/32 on blasts missing detectable serological specificities.
SUMMARY We have biochemically characterized by 2D (two‐dimensional) electrophoresis three novel class I molecules called A166, A149 and A216 expressed by 1591, a UV‐induced fibrosarcoma, and have compared them to class I molecules expressed by mice of the H‐2 q and H‐2 s haplotypes. A166 and A149 are very similar if not identical to D q and L q respectively. We have shown, using HPLC (high‐pressure liquid chromatography) tryptic peptide mapping, that the expression of A166 is approximately three fold greater than A149 , reminiscent of D d compared to L d . In addition A216 possess an identical isoelectric point to that of the K s molecule. We demonstrate that outbred Swiss Webster mice express an analogous constellation of class I molecules and we conclude that our results can be most easily interpreted in terms of an allogeneic origin for the novel class I molecules expressed on 1591.
SUMMARYSoluble class I molecules were immunoprecipitated from human sweat and serum using the BB7.7 monoclonal antibody (mAb) coupled to immunomagnetic beads. Molecules were analysed biochemically on SDS‐PAGE gels and finally by 1D‐isoelectric‐focusing (IEF). Serum‐ and sweat‐HLA IEF‐band patterns of the same individual were fully identical, showing that HLA excreted in sweat possess polymorphic structures like those in serum. Quantitatively, we used a highly sensitive competitive enzyme‐linked immunosorbent (ELISA) assay to determine soluble class I concentrations. The first group was that of non‐HLA‐A9 and ‐Bw62 sera, which were found to contain HLA levels with a mean concentration of 0.82 ± 0.63 μg/ml (n= 44). However, sera that were HLA‐A23 or −24 (splits of HLA‐A9) contained higher levels, with a mean of 3.2 ± 0.94 μg/ml (n= 20). Similarly, HLA‐Bw62 individuals had a higher mean of 2.05 ± 0.65 μg/ml (n= 10). The difference of the HLA‐A9 group to the first group was statistically highly significant, P < 0.0001, and that of the HLA‐Bw62 to the first was also significant, P < 0.004. Individuals who were both HLA‐A9 and ‐Bw62 (n = 5) did not express significantly higher levels than those who only had one of these specificities. Sweat HLA levels had a mean of 0.42 ± 0.4 μg/ml (n= 10). These results show for the first time that soluble class I peptides are excreted in relatively high concentrations in sweat and possess polymorphic structures identical to those of serum HLA and that serum HLA levels are allotype dependent.
SUMMARYIn DA strain rats, there are two other MHC class I loci (Pa and RT1.Fa) in the vicinity of the classical class I locus RT1.Aa. The Pa antigen is the pregnancy‐associated antigen, and it was detected by antibodies elicited in WF females pregnant by DA males without any other immunization. The Fa antigen was detected by a monoclonal antibody raised by alloimmunization. In the present work, the Aa, Fa and the Pa antigens have been compared by HPLC peptide mapping and by isoelectric focusing after their isolation by appropriate monoclonal antibodies. All the three antigens are identical in primary structure with respect to lysine, methionine, asparagine and the aromatic amino acid residues, but they differ from one another with respect to glutamic acid and/or aspartic acid residues. The PI values of the antigens differ slightly. All three antigens have two identical N‐linked glycans, but the Fa antigen has an additional N‐linked glycan. Based on the available amino acid sequence of the Pa antigen, it can be concluded that both Aa and Pa antigens are devoid of glycosylation in the second domain. This lack of glycosylation of the classical antigen Aa is unique for the rat, since classical class I antigens of the mouse show glycosylation in the first and second, and sometimes in the third domain, and those in the human, in the first domain only. The high degree of similarity among the Aa, Fa, and Pa molecules that this study indicates is also unique for the rat, since antigens encoded by different class I genes of the same haplotype are quite disparate in the mouse and human.
SUMMARY Although the molecular nature of several blood group antigens was established in 1950–1980, the identification and characteristics of the Rh‐antigens long remained unsolved. In 1982 two groups were able to conclusively identify the Rh 0 (D) antigen as a cell surface polypeptide with an apparent molecular weight of about 30 000. This protein has now been relatively well characterized. It seems to lack carbohydrate, it is strongly bound to the membrane skeleton, and it is posttranslationally modified by fatty acid acylation. Its NH 2 ‐terminal amino acid sequence has been determined. It is relatively hydrophobic, and its absence or decrease results in fragile erythrocytes or spherocytes. Its wide distribution in erythrocytes of various animals indicates that it plays an important physiological role.
Twenty-two subjects (11 HLA A1 B8 DR3, 11 non-A1 B8 DR3) were tested for the capacity of their lymphocytes to express Tac molecules and interleukin-2 (IL-2) receptors (quantified using radiolabelled IL-2) after mitogen stimulation. Ten of these subjects (five A1 B8 DR3 and five non-A1 B8 DR3) were also tested for the ability of their lymphocytes to proliferate under IL-2 stimulation. A1 B8 DR3 subjects express a normal number of high-affinity IL-2 receptor sites, but the affinity of these receptors sites is significantly increased. Unexpectedly, A1 B8 DR3 lymphoblasts show a lower response to IL-2 than non-A1 B8 DR3 for high doses of recombinant IL-2.
Twenty-five monoclonal antibodies (MABS) to complement components were evaluated according to the ISBT/ICSH protocol by twelve laboratories. Seven detected some form of C3c, but one of them, 174, did not react with EiC3b, although it was positive with 'EC3b' (Fruitstone). 174 may detect some form of enzyme sensitive C3b antigen, but C3a was not evaluated (present on 'EC3b' Fruitstone). Twelve of the antibodies were anti-C3d, one was an anti-C3g and five were anti-C4c.
SUMMARY The in vitro proliferative response of T cells primed with human thyroglobulin (Tg) was compared in 11 independent haplotypes on B10 background. B10.K and B10.S mice were the most responsive, whereas, with the exception of B10.PL ( H‐2 u , all other B10 congenics were intermediate responders. The two best responders to in vitro challenge with human Tg, of the k and s haplotype, are the same as those showing H‐2‐linked susceptibility to induction of experimental autoimmune thyroiditis (EAT) with mouse Tg. Since shared epitopes on human and mouse Tgs have been shown to be thyroiditogenic by adoptive transfer studies in CBA ( H‐2 k ) mice, the findings indicate that shared epitopes may be studied in appropriate (i.e. EAT‐susceptible) strains of mice. Therefore, we proceeded to develop methods to produce T‐cell lines and hybridomas to human Tg in B10.K and B10.S mice, test their cross‐reactivity to heterologous Tgs and their Ia restriction patterns. By using antigen‐presenting cells from recombinant strains, we identified restriction elements encoded by the I‐A subregion alone and a combinatorial molecule from the I‐AI/I‐E subregions.
SUMMARY A group of 30 Italian children affected by Dermatitis Herpetiformis (DH) was analysed for HLA region polymorphisms with both serological and DNA methods. Serological typing was performed on HLA‐A, B, C, DR, DQ antigens and C4A, C4B, Bf polymorphisms. DNA RFLPs obtained with TaqI enzyme were investigated with cDNA probes specific for DR beta, DQ alpha and DQ beta genes. The results were correlated with intestinal involvement and age at onset of the disease. The following observations were made: (1) the intestinal biopsies revealed a direct correlation between degree of lesions and age at onset of DH; (2) a significantly increased relative risk (RR) was found for the following HLA antigens: A1 (RR = 2.2), B8 (RR = 6.2), Cw7 (RR = 3.9), C4AQO (RR = 7.4), DR3 (RR = 5.2), DR7 (RR = 4.4), DRw53 (RR = 4.7), DQw2 (RR = 6.0); (3) B8 and DR3 were significantly more frequent in patients with severe intestinal lesions; and (4) of the two DR3 subtypes revealed by RFLP typing, only 3.1 showed an increased frequency in DH patients (RR = 8.4). It is suggested that the susceptibility to Juvenile DH is determined by the same genes, within the HLA region, that are associated with Coeliac Disease.
International Journal of ImmunogeneticsVolume 17, Issue 4-5 p. 279-299 ABO ANTIBODIES—SEROLOGICAL BEHAVIOUR AND IMMUNO-CHEMICAL CHARACTERIZATION R. Oriol, Corresponding Author R. Oriol Biochimie. Faculté de Pharmacie, Châtenay-Malabry, FranceR. Oriol, Biochimie, Faculté de Pharmacie, Wniversité de Paris Sud, F-92296 Châtenay-Malabry, France.Search for more papers by this authorB. E. Samuelsson, B. E. Samuelsson Department of Medical Biochemistry and Regional Blood Centre, Sahlgrenska Hospital, University of Göteborg, SwedenSearch for more papers by this authorL. Messeter, L. Messeter University Hospital Blood Centre, Lund, SwedenSearch for more papers by this author R. Oriol, Corresponding Author R. Oriol Biochimie. Faculté de Pharmacie, Châtenay-Malabry, FranceR. Oriol, Biochimie, Faculté de Pharmacie, Wniversité de Paris Sud, F-92296 Châtenay-Malabry, France.Search for more papers by this authorB. E. Samuelsson, B. E. Samuelsson Department of Medical Biochemistry and Regional Blood Centre, Sahlgrenska Hospital, University of Göteborg, SwedenSearch for more papers by this authorL. Messeter, L. Messeter University Hospital Blood Centre, Lund, SwedenSearch for more papers by this author First published: August 1990 https://doi.org/10.1111/j.1744-313X.1990.tb00880.xCitations: 47AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume17, Issue4-5August 1990Pages 279-299 RelatedInformation
Three HLA-DR3-linked polymorphisms of the DPA, DPB and DRB genes, previously associated with myasthenia gravis or coeliac disease, have been examined in Caucasian patients with Graves' disease. The patients did not differ from healthy DR3 subjects, indicating an absence of any association of Graves' disease with specific DR3 subtypes.
SUMMARY We assessed HLA‐DR types and investigated serum samples for islet‐cell cytoplasmic antibodies (ICA) in 31 Danish patients with chronic pancreatitis. The antigen frequencies were compared with those in 1177 unrelated healthy Danish controls. Twenty patients had insulin‐dependent diabetes and 11 had normal intravenous glucose tolerance. No significant differences in the frequencies of DR3, DR4, or DR2 were found between patients with insulin‐dependent diabetes and patients with normal glucose tolerance or between any of these groups and controls. ICA were negative in all patients with chronic pancreatitis. It is concluded that the beta‐cell dysfunction in insulin‐dependent diabetes in chronic pancreatitis differs from that of classical insulin‐dependent diabetes.
The ACI or BDIV rats responded with decreased or increased neutrophil levels in blood after the N-methyl-N-nitrosourea (MNU) administration. The F1 hybrids had decreased neutrophil counts, and the BDIV x (BDIV x ACI)F1 backcross offspring showed two phenotypes. The sex of the rats and the neutrophil response to MNU assorted independently. The results indicated that the neutrophil response to MNU was regulated by autosomal gene Nrm-1 with two alleles. The Nrm-1d regulates the decrease and the Nrm-1i regulates the increase of neutrophils in blood after the MNU administration. The results were confirmed by the SKUMIX computer program. We found that the Nrm-1 gene was linked to the agouti locus (chi-square = 10.3, P less than 0.001). The map distance between two genes was 33 +/- 5 cM. The Nrm-1 gene thus resides on the linkage group IV of the rat.
