bluuebunny/crossref_metadata_2025 huggingface dataset:
FUNCTIONAL ROLES OF HUMAN CLASS II ANTIGENS IN T CELL PROLIFERATIVE RESPONSE COMPARISON OF THE DR AND DQ MOLECULES USING MOUSE MONOCLONAL ANTIBODIES
Authors: Chen R.‐F. , Maeda H.
Published: April 2007

The monoclonal antibody (mAb) NC1 recognizing a monomorphic DR determinant and the anti‐DQ mAbs PLM2, PLM9, and PLM12 recognizing polymorphic DQ determinants were produced. NCI reacted with the Hl Ll (DR) and H1L2 (DRw52, DRw53 and allelic products) complexes of a DR family, while the specificity of PLM12 was DQw3 (previously called TB21). Both PLM2 and PLM9 reacted with the allodeterminant of TAlO (a subtype Of DQw3). These three mAbs immunoprecipitated the same H2L3 complex of a DQ family. With the aid of these mAbs, DR molecules but not DQw3 molecules were detected on monocytes in significant quantities. The functional roles of these class II molecules in the T cell proliferative responses to three soluble antigens (PPD, mite, Candida) and alloantigens were examined by blocking assays in vitro. NCI almost completely inhibited T cell proliferative responses against both soluble antigens and allogeneic antigens. In contrast, PLM2, PLM9 and PLM12 showed no significant inhibitory effects at all. These results indicate that DR and DQ antigens are different in their functional roles as well as their serological and immunochemical characteristics and tissue distributions; these three soluble antigens and the alloantigen were presented in association with determinants residing predominantly on two forms of NCl‐reactive molecule, namely the H1L1 and/or HlL2 complex of a DR family but not in association with the DQw3 allodeterminant on the H2L3 complex of a DQ family.
ASSOCIATION BETWEEN HUMAN IgM AUTOANTIBODIES AND κ CHAIN ALLOTYPES
Authors: Goni F. R. , Frangione B.
Published: April 2007

The relationship between the immunoglobulin kappa light chain allotypes and autoantibodies was studied in a series of seven human monoclonal kappa‐bearing IgM antibodies with Rheumatoid Factor (RF) activity, two IgM anti‐low density lipoprotein (LDL) antibodies, and one IgM anti‐intermediate filament (IF) antibody. Residues at amino acid positions 153 and 191 related to the Km allotypes in human kappa chains were determined by an HPLC tryptic fingerprint and corroborated by amino acid sequence analysis. All the autoantibodies shared similar variable regions derived from the V gene(s). The seven RF and the anti IF were associated with the Km(3) constant region allotype whereas the two antiLDL were associated with the Km(1,2) allotype. Thus, monoclonal autoantibodies showed the same Km allotypic distribution as the normal population. However, although the number of samples is small, it seems likely that a preferential association may exist between particular V, genes and Km alleles in the generation of autoantibodies with different specificities.
MOLECULAR COMPLEXITY OF Qa‐2 ANTIGENS DEMONSTRATED BY TWO‐DIMENSIONAL GEL ELECTROPHORESIS
Authors: Robinson P. J. , Lefkovits I. , Lindahl K. Fischer
Published: April 2007

Biosynthetically labelled Qa‐2 antigens were isolated from mouse spleen cells by immunoprecipitation with anti‐Qa‐2 antisera. When newly synthesized Qa‐2 molecules from several different inbred strains were analysed by two‐dimensional (2D) gel electrophoresis; four different phenotypes were observed that differed in the number of polypeptides present. The ability to distinguish Qa‐2+ phenotypes was used to map the recombination points in two congenic strains, B6. Tlaa and A. Tlab. No alternative Qa‐2‐like polypeptides were detected in B6.K1 (Qa‐2−) cells using a polyspecific rabbit antiserum against mouse class I antigens, but a new molecule was detected in BALB/cBy (Qa‐2−) cells. Pulse‐chase and surface‐labelling experiments showed that some, but not all, of the newly synthesized Qa‐2 precursor forms are processed to mature cell surface molecules.
HETEROGENEITY OF STEROID 21‐HYDROXYLASE GENES IN CLASSICAL CONGENITAL ADRENAL HYPERPLASIA
Authors: Dawkins R. L. , Martin E. , Kay P. H. , Garlepp M. J. , Wilton A. N. , Stuckey M.S.
Published: April 2007

Careful genotyping of three families, each having a member with classical salt‐losing steroid 21‐hydroxylase deficiency, has allowed identification of carrier haplotypes. Digestion with TaqI or EcoRI and probing with a cDNA probe for the 21‐hydroxylase genes (pC21/3c) revealed that all six affected haplotypes are abnormal with at least EcoRI. The data suggest that there is extreme polymorphism of the 21‐hydroxylase genes and that dysfunction may result from several different abnormalities.
GENERAL CONSIDERATIONS IN THE INTERPRETATION OF I‐J GENETIC RESTRICTIONS: EVIDENCE THAT THE ANTIGEN‐BINDING CHAIN OF ANTIGEN‐SPECIFIC T‐SUPPRESSOR FACTOR HAS TWO RECOGNITION SITES FOR MEMBERS OF THE I‐J HIERARCHY
Authors: Asherson G. L. , Zembala M. , Romano G. Colonna , Colizzi V.
Published: April 2007

(CBA × B10)F1 [(H‐2k x H‐2b)] mice produce two types of antigen‐specific T‐suppressor factor (TsF), which can be separated by affinity chromatography on anti‐I‐J monoclonal antibody. After reduction and alkylation, both chains of F1 TsF are required for biological activity. However, the antigen‐binding chain (AgBC) of F1 TsFk (AgBCk) is only complemented by I‐Jk and likewise for F1 TsFb. In other words, interchain complementation shows the same genetic restriction in interchain complementation in parental and F1 mice. F1 TsF bearing, for example, I‐Jk (TsFk), interacts with haptenized ‘antigen‐presenting cells’ (‘APC’) of both parental haplotypes, and may be described as showing dual reactivity. In contrast, it is known that parental TsF shows single reactivity, and only interacts with haptenized ‘APC’ of the parental haplotype. The combination of F1 AgBCk and parental I‐Jk chains interacts with haptenized ‘APC’ of both parental haplotypes (dual reactivity). In contrast, the combination of parental AgBCb and F1 I‐Jb shows single reactivity and only interacts with haptenized ‘APCb’. It was inferred that the antigen‐binding chain is responsible for the dual reactivity and, hence, for the interaction with a member of the I‐J hierarchy on the ‘APC’. It was concluded that the antigen‐binding chain of TsF has two recognition sites for members of the I‐J hierarchy—one for interchain complementation and the other for interaction with the haptenized ‘antigen‐presenting cell’. The term member of fhe I‐J hierarchy is used instead of I‐J because it is not clear whether the AgBC interacts with I‐J or a receptor for I‐J, or indeed a receptor for that receptor.
ASSOCIATION OF GOITROUS AUTOIMMUNE THYROIDITIS WITH HLA‐DR3 IN EASTERN HUNGARY
Authors: Stenszky V. , Balázs C. , Kraszits E. , Juhasz F. , Kozma L. , Balázs G. , Farid N. R.
Published: April 2007

An association of HLA‐DR5 and goitrous autoimmune thyroiditis has been reported elsewhere (Farid et al., 1981; Weissel et al., 1980). Recently, the disease was found to be associated with HLA‐DR4 in Newfoundlanders (Farid & Thompson, 1986). In order to find out whether different HLA associations with the disease may be found in different ethnic groups, we have now typed 68 patients with autoimmune goitrous thyroiditis from Eastern Hungary for HLA‐A, ‐B, ‐C, and ‐DR antigens; 66 of these patients were also typed for IgG heavy‐chain markers (Gm). A significant increase in DR3 (OR = 3·30) and a non‐significant increase in DR4 (OR = 1·67) were found in the patients when compared with controls. The Gm3 allele, g, interacted with DR3 to enhance the risk for goitrous autoimmune thyroiditis. Hashimoto's disease may show different associations in different ethnic groups, and indeed within the same ethnic group, when newly diagnosed patients are typed several years apart.
Ir GENE FOR BOVINE INSULIN IN THE RAT MAPS TO RT1.Bβ
Authors: Mizuno K. , Inomata T. , Tsuchimoto S. , Matsuno Y. , Niiyama T. , Fujii H. , And T. Natori , Aizawa M.
Published: April 2007

The genetic control of the immune response to bovine insulin (BI) in the rat was investigated. As a result of experiments utilizing two intra‐MHC recombinant rats and of blocking experiments with monoclonal antibodies against MHC class II antigens, an immune response gene for BI in the rat could be mapped to the RT1.Bβ locus.
THE ASSOCIATION OF DNA VARIANTS AT OR NEAR THE IgH LOCUS WITH RHEUMATOID ARTHRITIS
Authors: Sakkas L. I. , Demaine A. G. , Vaughan R. W. , Welsh K. I. , Panayi G. S.
Published: April 2007

DNA samples from 78 patients with classical or definite rheumatoid arthritis (RA) and 132 healthy controls were analysed by the Southern blotting method, using two DNA probes: the first to the immunoglobulin μ heavy‐chain switch region (Sμ), in conjunction with the SstI restriction endonuclease, and the second to the D14S1 region, in conjunction with the HindIII restriction endonuclease. The homozygous phenotype for the 6·9 kb Sp fragment was decreased in the patient group (7·8%) compared to controls (19·1%) (P= 0·04). The homozygous phenotype for the 10·3 kb D14S1 fragment was increased in the patient group (38·5%) compared to controls (21·2%) (P= 0·02). The increase was more pronounced in the DR4‐positive patients (51·2%) (P versus DR4‐positive controls = 0·009). These results suggest that genes on chromosome 14 are involved in the genetics of RA.
VITAMIN A‐ENHANCED CLEFT PALATE SUSCEPTIBILITY ASSOCIATED WITH H‐2
Authors: Tyan M. L.
Published: April 2007

Pregnant mice from the congenic strains C57BL/10Sn, B10.BR, B10.A/SgSn, B10.A(SR)/SgSn, B10.A(2R)SgSn and B10.A(18R)Sg were fed Purina Laboratory Chow or the same diet plus approximately 400IU vitamin A daily and given 80 mg/kg dexamethasone intra‐peritoneally or a sham injection on the 12th day of pregnancy. It was found that only strains with b alleles between H‐2S and H‐2D had significantly higher frequencies of isolated cleft palate among their progeny when fed the supplemental vitamin A. The locus appears to be on the centromeric side of a dexamethasone‐induced cleft palate gene which has been mapped to the same general area.
COMPLEXITY OF THE Rh ANTIGEN DEMONSTRATED BY COMPARATIVE TESTS USING ANTISERA OF HUMAN AND PRIMATE ORIGINS
Authors: Socha W. W. , Rouger P. , Ruffié J. , Moor‐Jankowski J.
Published: April 2007

Comparative analysis of two antisera, one produced in chimpanzee and another of human origin, demonstrates the existence of a spectrum of antibodies directed against at least four antigenic determinants connected with Rh reactivity. Some of the determinants are shared by chimpanzee and human red cells, while others are restricted to one species only. Based on this study, it is suggested that both the human Rh(D)‐positive type and its chimpanzee counterpart, the Rc‐positive type, could be of common origin, while the negative types are the results oflater, parallel events during evolution.
A JAPANESE PATIENT WITH THE RARE Rhnull PHENOTYPE OF THE ‘REGULATOR TYPE’
Authors: Kishi K. , And T. Yasuda , Uchida M.
Published: April 2007

An example of red cells having no reaction with any Rh antisera was found in a Japanese woman. Results of a serological investigation of the family indicated the action of a ‘regulator’ gene. Her serum contained an antibody which agglutinated all cells of common Rh types, except for Rhnull, by the saline, anti‐globulin and papain techniques.
ASSOCIATION BETWEEN RESTRICTION FRAGMENT LENGTH VARIANTS OF THE COMPLEMENT C4 GENES AND MHC HAPLOTYPES
Authors: Partanen J.
Published: April 2007

DNA polymorphism of the human major histocompatibility complex (MHC)‐linked complement C4 genes was studied using restriction enzymes XbaI and TaqI, and Southern hybridization. The results show that some, but not all, C4 phenotypes can be divided into subtypes. Analysis of MHC haplotypes indicates that in each extended MHC haplotype, i.e. in the haplotypes having a particular combination of HLA and complotype phenotypes in significant linkage disequilibrium, the C4 genes always produce just one ‘conserved’ restriction enzyme fragment pattern, while in the other haplotypes the C4 genes are more heterogeneous. Furthermore, the findings provide preliminary evidence for a C4B gene duplication, and suggest that the C4 genes may often be ‘corrected’ alike.
HLA ANTIGENS IN SICILIAN PATIENTS AFFECTED BY CHRONIC MYELOGENOUS LEUKAEMIA
Authors: Caruso C. , Campo P. Lo , And C. Botindari , Modica M. A.
Published: April 2007

HLA antigens were investigated in Sicilian patients with chronic myelogenous leukaemia (CML) and in Sicilian healthy controls. The frequency of the HLA‐DRw6 antigen was significantly decreased in the group of patients. These results suggest that DRw6 may be a marker for decreased susceptibility to the etiological or pathogenic mechanism(s) which produce CMLs.
ASSIGNMENT OF THE Es‐6 LOCUS TO LINKAGE GROUP VII OF THE RAT (RATTUS NORVEGICUS) BY THE USE OF HXB RECOMBINANT INBRED RAT STRAINS
Authors: Pravenec M. , Křen V. , Klír P.
Published: April 2007

The Es‐6 locus is assigned to linkage group VII of the rat, which consists of three loci, coding for a morphological trait, a histocompatibility antigen and an isozyme polymorphism. The linkage between Es‐6 and the lx locus seems to confirm the previously suggested homology between Es‐6 and the mouse Es‐17 locus and may indicate homology between lx and the mouse lu locus.
HIGH FREQUENCY OF Mlsa‐REACTIVITY AMONG Ab‐RESTRICTED, H‐Y‐SPECIFIC T CELL CLONES
Authors: Frangoulis B. , Klein J.
Published: April 2007

A high frequency (80%) of Ab‐restricted, H‐Y‐specific T cell clones, but not of Ab‐restricted LDH‐B‐specific T cell clones, was found to be Mlsa‐reactive. This reactivity could be inhibited by class II (A and E)‐specific antibodies, and required an E‐positive stimulator cell. The proliferation was also blocked by T cell receptor‐specific and by CD4‐specific antibodies. Possible interpretations of these findings are discussed.
AUGMENTED IN VITRO PRESENTATION OF Mls DETERMINANTS AFTER ANTI‐IMMUNOGLOBULIN‐INDUCED B CELL ACTIVATION: ONTOGENY AND ROLE OF PURIFIED B CELLS
Authors: Ryan J. J. , Thompson C. B. , Mond J. J. , Finkelman F. D.
Published: April 2007

Murine splenocytes which contained B cells activated by in vivo exposure to affinity‐purified goat anti‐mouse IgD (GaMD) antibody were utilized to present major histocompatibility complex (MHC) and non‐MHC minor lymphocyte‐stimulating (Mlsa) determinants in a primary mixed lymphocyte reaction (MLR). As the time in hours after in vivo exposure to GaMD increased, splenocytes from adult mice showed a co‐ordinate increase in cell size, expression of public and private MHC class II antigenic determinants and MHC and Mlsa antigen‐presenting capacity. This augmented alloantigen‐presenting capacity was demonstrable with either irradiated or mitomycin C‐treated adult splenocytes. In contrast, GaMD‐treated neonatal splenocytes from 10‐day‐old mice demonstrated no significantly increased class II expression or enhanced MHC stimulatory capacity, but nevertheless triggered augmented responder cell proliferation across an Mlsa barrier. Thus, increased class II expression or presenting capacity may not be required for an augmentation in splenocyte Mls‐stimulating ability to occur. In vitro exposure of T cell‐depleted splenocytes or highly purified small resting B cells to GaMD or lipopolysaccharide (LPS) induced a substantially increased ability in those populations to present MHC and Mlsa antigens in a primary MLR. Hence in vivo or in vitro activation of B lymphocytes in a stimulator cell population may yield more effective presentation of MHC and non‐MHC determinants.
DIFFERENTIAL EXPRESSION OF THE ASGM1 ANTIGEN ON ANTI‐REOVIRUS AND ALLOREACTIVE CYTOTOXIC T LYMPHOCYTES (CTL)
Authors: Parker S. E. , Sun Y. H. , Sears D. W.
Published: April 2007

Anti‐reovirus cytotoxic effectors were found to be: (i) H‐2 restricted; (ii) virus specific; (iii) non‐lytic (in 4 h) for natural killer (NK)‐sensitive YAC‐1 cells; and (iv) positive for the Thy‐1 and Lyt‐2 lymphocyte markers. Thus, anti‐reovirus cytotoxic effectors have the functional and phenotype characteristics of cytotoxic T lymphocyte (CTL). A significant fraction of anti‐viral CTL, as well as alloreactive CTL, were also found to be positive for the asialo GM1 (ASGM1) cell surface antigen, generally considered to be a NK cell marker. ASGM1 expression on these CTL, as determined by sensitivity to antibody plus complement (C), appeared to be highly variable and dependent on two factors—the nature of the antigenic stimulus (viral vs. alloantigen), and the mouse strain from which the CTL originated. Thus, ASGM1 antigen expression on CTL appears to be regulated and may be under the control of lymphokines, development differentiation signals and/or other strain‐dependent genetic factors.
A STUDY OF HLA‐A, B, DR and Bf5 BEARING HAPLOTYPES DERIVED FROM 304 FAMILIES RESIDENT IN THE NORTH WEST OF ENGLAND
Authors: Davidson J. A. , Kippax R. L. , Dyer P. A.
Published: April 2007

We report here haplotype frequencies for class I (HLA‐A, B), class III (HLA‐DR) and class III (Bf) gene products of the major histocompatibility complex (MHC) of man. As in other studies (Bertrams & Baur, 1979; Grange et al., 1981), we have chosen to document all families typed for HLA antigens and Bf phenotypes irrespective of ascertainment. We obtained 1,094 haplotypes from 304 families resident in the North West of England, of which 34·1% had been fully typed for HLA‐A,B,DR and Bf polymorphisms. We have been able to find both positive and negative linkage disequilibria for two and three locus haplotypes and have listed the most commonly occuring four locus haplotypes. Our data confirms the position of the complement group between HLA‐B and HLA‐DR, and we have looked for evidence of segregation distortion of MHC haplotypes.
A NEW DUPLICATION AT THE C4B LOCUS ASSOCIATED WITH THE HLA‐Aw68, Cw8, Bw65 HAPLOTYPE
Authors: Borelli I. , Crepaldi T. , Frattasio C. , Curtoni E. S.
Published: April 2007

A family with a cross‐over between HLA‐B and HLA‐DR was analysed for its complement alleles. This allowed location of the cross‐over between HLA‐B and C4. Furthermore, the same family showed a previously undescribed duplication at the C4B locus (C4B*2,2) that was associated with the HLA‐Aw68, Cw8, Bw65, C2*1, Bf*S, C4A*2, DR7, DQw2 haplotype.
AN ANALYSIS OF THE EFFECT OF HLA‐DP IN THE MIXED LYMPHOCYTE REACTION
Authors: Farrell C. , Honeyman M. , Hoadley C.
Published: April 2007

It has recently been reported that HLA‐DP antigens may play an important role in the development of graft‐versus‐host disease (G VHD) following transplantation of haploidentical bone marrow as a treatment for haematological malignancies. Mixed lymphocyte culture (MLC) is routinely performed prior to bone marrow transplantation to assess the suitability of the donor, and we have therefore examined the role of HLA‐DP in this test. One‐way MLC chequerboard experiments were performed between 17HLA‐Dw3homozygous typing cells (HTC) with a range of HLA‐DP antigens represented, including HLA‐DPw1, w2, w3, w4 and CP63. The experiments were performed on multiple occasions and each time a highly significant difference (P= <0.001) was observed between the Relative Responses (RR) in the HLA‐DP matched responder/stimulator pairs and the HLA‐DP mismatched pairs. There was, however, considerable overlap in these results with ranges in the HLA‐DP‐matched group RRs of 0–17%, and 0–62% in the mismatched group. Only 3.1% of the HLA‐DP‐matched group had a RR>5%, while 48% of the HLA‐DP mismatched group had a RR>5%. From these results it was calculated that a positive response (> 5%) has a 96% chance of being due to an HLA‐DP disparity of one or two antigens. Conversely, with a negative MLC the chance of their being no HLA‐DP antigen disparity was only 65%. From these results we conclude, firstly, that HLA‐DP has a significant influence on the MLC. Secondly, it is clear that a negative MLC does not necessarily indicate identity at theHLA‐DPlocus. An increased incidence of bone marrow transplants mismatched atHLA‐DPwould be expected from increased use of phenotypically identical, but unrelated, donors and related donors sharing only one haplotype with the recipient. It would thus seem important to consider the HLA‐DP type of all patients and potential donors prior to bone marrow transplantation, since a negative MLC is not sufficient to eliminate HLA‐DP disparity.
THE ANTIGENIC DETERMINANTS, Rg/Ch/WH, EXPRESSED BY JAPANESE C4 ALLOTYPES
Authors: Giles C. M. , Tokunaga K. , Zhang W. J. , Tanaka H. , Endoh N. , Juji T.
Published: April 2007

The expression of antigenic determinants, Rg/Ch/WH, on Japanese C4 allotypes has been studied. Although the Japanese C4 allotype frequencies are known to differ from Europeans, the antigenic expression of their C4 allotypes correlates with associations described previously. All 89 random donors and 17 selected donors were Rg:1,2 so neither Rg:1,−2 nor Rg:−1,−2 was found. The frequency of Ch: 1,−2,3 was elevated while that of Ch: 1,2,3 was reduced, which was seen as a direct result of the higher frequency of B2 and B5 allotypes. None of the Japanese were Ch: 1,2,−3, but this can be accounted for by the absence of the A*6,B*1 haplotype. The WH determinant, which has been associated completely with Rg:1,−2 in Caucasians, was found at a higher frequency, 32%, in association with an A*3,2,B*QO haplotype expressing Rg:1,2, which has not been described previously. Detailed investigation showed that the A3 allotype was Rg:1,2 whereas the A2 allotype only expressed Rg1 (Rg:1,−2 WH+).
CORRELATION OF IgA2 SERUM LEVELS IN PARENT‐OFFSPRING PAIRS
Authors: Benedictis G. De , Rose G. , Brancati C.
Published: April 2007

IgA2 serum levels were measured by ELISA in 120 healthy subjects from 40 nuclear families (both parents and one offspring). No sex‐associated difference was observed. Moreover, the IgA2 serum levels proved to be significantly correlated in parent‐offspring pairs (r=0·55; P < 0·001), while there was no significant correlation in mother‐father pairs of the same family. The data suggest that the serum level of the IgA2 subclass is genetically controlled.
THE EXPRESSION OF MURINE ALLOANTIGENS ON BLOOD LYMPHOCYTES
Authors: Scott B. M. , Hogarth P. M. , Scollay R. , McKenzie I. F. C.
Published: April 2007

Single‐ and two‐colour immunofluorescence was used to analyse and compare the expression of 12 antigens on the surface of Ig− mouse blood lymphocytes (BL) and Ig− lymph node (LN) cells. Studies in different strains of mice showed that: (i) there were fewer Thy‐1+, Ly 1+, L3T4+ cells in BL compared to LN; (ii) Ly 2+ BL showed a unique fluorescence profile with a temporal variation in antigen density not evident in LN; (iii) Thy‐1− Ly 1−cells were more common in BL than LN; (iv) L3T4 and Ly 2 were present on mutually exclusive subpopulations in BL; (v) Ly 6A, (Ly 6.2), Ly 6C (Ly 28.2) Ly 28.6C and Ly 12.1 antigenic determinants were expressed on the same proportion of BL and LN cells and to the same level; (vi) Ly 24 (Pgp‐1) was the only alloantigen examined where the number of positive cells was increased in BL (65%) compared to LN (40%); (vii) Ly 5 and Ly 15 (LFA‐1) showed significant differences in antigen density distribution between BL and LN; (viii)Ly 21.2 was similar to Ly 15.2 expression; (ix) 20% of Ig−LN cells were Ia+, but la was absent from Ig−BL. Thus, BL differ in antigen distribution and density from lymphocytes in LN and other tissues and should be considered as a unique population of lymphocytes.
H‐Y RESPONSES OF NON‐OBESE DIABETIC (NOD) MICE
Authors: Chandler P. , Fairchild S. , Simpson E.
Published: April 2007

Female non‐obese diabetic (NOD) mice were tested for their ability to make responses to the male‐specific (H‐Y) transplantation antigen. In vivo assessment of this ability was made using skin graft rejection. A proportion (60%) spontaneously rejected NOD male tail skin by 80 days post‐transplantation. The detection of the generation of H‐Y‐specific cytotoxic T cells, following in vivo priming and secondary in vitro restimulation, was carried out using a conventional 51Cr release assay. Female NOD mice primed either by skin grafting, intraperitoneal (i.p.) or footpad (f.p.) injection of male NOD spleen cells could be induced to make anti‐H‐Y cytotoxic responses, but not every immunized mouse responded. The nature of the H‐Y‐reactive T cells was investigated further by the in vitro isolation of T‐cell clones of which some were H‐Y specific.
MODULATION OF ALLOTRANSPLANTATION TOLERANCE INDUCTION BY INTERLEUKIN‐1 AND INTERLEUKIN‐2
Authors: Holáň V.
Published: April 2007

Transplantation tolerance was induced in mice by inoculating newborn animals with semi‐allogeneic haematopoietic cells. The mice rendered tolerant were treated within the first week of birth, or at the time of grafting (age 7–8 weeks), with recombinant interleukin‐1 (rIL‐1) or interleukin‐2 (rIL‐2). The effects of these treatments on tolerance induction were monitored in terms of skin allograft survival. Treatment of newborn mice with rIL‐2 abolished tolerance induction in nearly all tested animals. When administered at the time of grafting, both rIL‐1 and rIL‐2 decreased the proportion of tolerant animals. However, these modulation effects of interleukins were only observed in strain combinations with genetic differences at the K end of H‐2 or in the entire H‐2 complex, in which it is difficult to establish permanent tolerance; no effects of interleukins on tolerance induction were found in a strain combination with a relatively weaker genetic barrier represented by incompatibility at the D region of the H‐2 complex.
GENETIC CONTROL OF BLOOD NEUTROPHIL CONCENTRATION IN THE RAT
Authors: Stolc V.
Published: April 2007

Two phenotypes that characterize low and high neutrophil concentrations in blood were found in the rat. It is possible that either two regulating alleles control the high (Nr‐1a) and the low (Nr‐1b) neutrophil concentration or that a polygenic system affects the neutrophil concentration in blood. The F1 hybrids of four intercrosses had low neutrophil levels in blood that suggested a dominant effect of the Nr‐1b allele. The backcross progeny showed abnormal segregation of the neutrophil phenotypes. The high phenotype was expressed in only 5% of the offspring. The presence of the two phenotypes and their distribution in the backcross progeny was confirmed by the computer program SKUMIX that resolved the quantitative traits into two discrete distributions with 95% and 5% representation. Because the logistic of SKUMIX can not rule out the polygenic effect, only further breeding studies using linked markers can resolve the mechanism of the genetic control of neutrophil concentration in the rat.
EXPRESSION OF ABH, LEWIS AND RELATED TISSUE ANTIGENS IN THE HUMAN THYMUS
Authors: Pendu J. Le , Dalix A.M. , Mollicone R. , Crainic K. , Oriol R.
Published: April 2007

Expression of ABH, Lewis and related antigens was studied in the thymus of children of known ABO, Lewis and secretor status using a panel of specific reagents. ABH and Lewis antigens partly under control of the secretor status were expressed on the Hassals' bodies and a large fraction of the medullary epithelial cells. The sialyl‐Lea antigen was only present on some Hassals' bodies of Lewis‐positive individuals. ABH but not Lewis antigens were also present on cortical epithelial cells but this was independent of the secretor status. The X, sialyl‐X and Y antigens were only expressed on Hassals' bodies irrespective of the ABO, Lewis or secretor phenotype. Furthermore, the anti‐X and sialyl‐X antibodies labelled a subset of leucocytes of all the individuals tested. These results show that the genetic control of the expression of ABH and Lewis glycosidic tissue alloantigens in the thymus is different on cortical and medullary epithelial cells and stress the heterogeneity of the thymus epithelial cells.
CROSS‐LINKING OF Ly 6‐LINKED ALLOANTIGENS: ASSOCIATION BETWEEN ThB AND Ly 5
Authors: Houlden B. A. , McKenzie I. F. C. , Hogarth P. M.
Published: April 2007

The bifunctional cross‐linking reagent dithiobis (succinimidyl propionate) (DSP) was used to cross‐link 125I surface‐labelled glycoproteins from viable thymocytes. The cells were solubilized, and the cross‐linked material immunoprecipitated and analysed by SDS‐PAGE. When DSP cross‐linked thymocyte material was immunoprecipitated with either anti‐ThB or anti‐Ly 5 monoclonal antibodies, and then cleaved, molecules with masses identical to Ly 5 (Mr180 kD) and ThB (Mr 16–18 kD) were obtained. However, if the cross‐linker was not cleaved, the intact product had a molecular mass of > 200 kD. The identity of these co‐precipitated, cross‐linked moieties was formally proved by limited proteolysis peptide map analysis. The data indicated that the ThB and Ly 5 antigens were associated on the thymocyte cell surface but no such association could be found on peripheral lymphocytes. The ThB‐Ly 5 interaction may indicate an association relevant to the differentiation of thymocytes.
THE INFLUENCE OF THE BoLA‐A LOCUS ON REPRODUCTIVE TRAITS IN CATTLE
Authors: Stear M. J. , Pokorny T. S. , Echternkamp S. E. , Lunstra D. D.
Published: April 2007

Associations between the major histocompatibility complex (MHC) and reproductive performance have been reported in humans, mice, rats, pigs and chickens. Only the A locus of the bovine major histocompatibility complex (BOLA‐A) has been well characterized, and 42 alleles of this locus have been identified in American cattle. Four studies were conducted to examine the association between alleles of the BoLA‐A locus and reproductive performance. Testis size, which is an indicator of early puberty and increased fertility in young bulls, was examined in 440 yearling bulls from nine breeds with a gene substitution model that included the effects of breed, sire, age of dam and age or weight of the bull. Estimated breeding value for twinning was examined with a gene substitution model with 204 cattle from a herd with a high frequency of twinning. Fertility of potential partners having BOLA‐A locus alleles in common was examined in a prospective study involving 101 pure‐bred Hereford cows mated by artificial insemination to four pure‐bred Hereford bulls. The effect of homozygosity on birth weight, pre‐weaning weight gain and post‐weaning weight gain was estimated in a sample of 683 calves from nine breeds; 22% of the calves were apparently homozygous and 78% were heterozygous at the BOLA‐A locus. There were significant and large effects of some BOLA‐A locus alleles on paired testicular volume, but the analyses on the other traits did not show significant associations. Substitution of the W6.1 allele for the W9A allele reduced paired testicular volume by 150 & 44 cm3. The W6.1 allele has now been shown to influence a reproductive trait, a production trait and susceptibility to an economically important disease. Selection for these traits may influence the frequency of the large number of alleles at the BOLA‐A locus.
T‐CELL DEPLETION OF HUMAN BONE MARROW
Authors: Gee A. P. , Mansour V. , Weiler M.
Published: April 2007

The myelo‐ablative effects of high‐dose therapy for refractory cancer can be overcome by the transplantation of bone marrow from an HLA‐matched normal donor. Suitable donors are available for only one patient in three, and even minor disparities at HLA loci can produce graft‐versus‐host disease (GvHD) in transplant recipients. Depletion of T lymphocytes from the marrow in vitro can reduce the incidence and severity of GvHD.

In this paper we review the use of immunomagnetic cell separation for the depletion of mature T cells from bone marrow. This procedure uses monoclonal antibodies to identify the target cells. These are then rosetted with anti‐immunoglobulin‐coated paramagnetic microspheres and collected by exposure of the marrow to a magnetic field. Factors impacting the efficiency of the separation, including choice of anti‐immunoglobulin and monoclonal antibodies, incubation conditions and methods for residual cell detection, are outlined.

The relative limitations and advantages of the method are discussed in relation to other techniques. It is concluded that the flexibility of the immunomagnetic procedure, in its ability to be used for both positive and negative selection of T‐cell subsets, or for pan‐T‐cell depletion, could make it the method of choice in this application.
ALLOTYPING FOR HLA CLASS I USING PLASMA AS ANTIGEN SOURCE
Authors: Grosse‐Wilde H. , Doxiadis I.
Published: April 2007

Immunoadsorption of soluble HLA class I antigens onto immunobeads, one‐dimensional iso‐electric focusing of these proteins and subsequent immunoblot‐ting allows a biochemical identification of HLA class I allotypes. The distinct protein bands can be clearly attributed to particular HLA antigens and are comparable to those observed after detergent solubilization of membrane‐bound HLA antigens. Segregation analysis showed that the biochemically detected pattern of soluble class I gene products followed Mendelian inheritance. However, antigens such as HLA‐A1, ‐A2, ‐B8, and ‐B51 were not always clearly detectable, a phenomenon attributable to either different plasma concentrations of these HLA antigens or variable affinity of the monoclonal antibody used to capture class I antigens. These results show that in principle allotyping of HLA class I using plasma as the antigen source is feasible, but with the limitation that some antigens may not be easily detected in some individuals.
POSITIVE SELECTION OF Tac‐ (CD25) POSITIVE CELLS FOLLOWING T‐CELL ACTIVATION: USE OF IMMUNOMAGNETIC SEPARATION AND IMPLICATIONS FOR T‐CELL CLONING
Authors: Lundin K. E. A. , Ovigstad E. , Sollid L. M. , Gjertsen H. A. , Gaudernack G. , Thorsby E.
Published: April 2007

We have investigated if positive selection for cells expressing activation antigens, which appear on the cell surface during T‐lymphocyte activation, could be used for cloning purposes. For this purpose, we used paramagnetic, monodisperse Dynabeads coated with anti‐Tac monclonal antibody, which recognizes CD25 (interleukin‐2 receptor light chain). After the first 6–12 h of a primary response, depletion of Tac+ cells could largely abrogate the specific response. This indicated that the specifically responding cells were found among the Tac+ population. T‐cell cloning was thus performed on Tac+ blasts positively selected after 18 h of a primary response, at day 6 of a primary response or during secondary stimulation, and gave a high percentage of specific clones. This method is thus a good alternative to established techniques.
mAb KUL/05 IDENTIFIES A DENATURATION‐RESISTANT DETERMINANT SHARED BY CLASS II MHC PRODUCTS DR, DQ AND DP
Authors: Giacomini P. , Tecce R. , Nicotra M. R. , Cohen B. B. , Mazzilli M. C. , Natali P. G.
Published: April 2007

mAb KUL/05, a novel murine monoclonal antibody, reacts with molecules displaying the typical tissue distribution and molecular profile of class II MHC antigens. An extensive scrutiny employing serological and immunochemical assays on DR homozygous and DRα‐ mutant cell lines has shown that this reagent displays some additional, interesting features, namely mAb KUL/05 (a) binds in a broadly monomorphic fashion to cells of DR1 through seven specifities, (b) recognizes a determinant shared by a large proportion of DR, DQ and DPβ chains from most haplotypes, in both their monomeric and α chain‐associated forms, and (c) reacts with frozen, acetone‐fixed, as well as conventional, formalin‐fixed, paraffin embedded tissues. Thus, mAb KUL/05 is likely to represent a useful adjunct for the study of the expression of class II MHC products in normal and pathological tissue specimens.
IMMUNOGENETIC STUDIES OF SPONTANEOUS ABORTION IN MICE: III. NON‐H‐2 ANTIGENS AND GESTATION
Authors: Bobé P. , Kiger N.
Published: April 2007

CBA/J (H‐2k) females, mated with DBA/2 J (H‐2d) or DBA/1 J (H‐2q) males, exhibit a high rate of fetal resorption. In contrast, when H‐2 identical CBA substrains (i.e. CBA/Ca and CBA/N) are used, this phenomenon is not observed. On the other hand, before mating with DBA/2 J males, pre‐immunization of CBA/J females with spleen cells coming from BALB/c J or (DBA/2 x BALB/c J) F1 males (and not from other H‐2d identical males whatever their Mls alleles) has significantly decreased the fetal resorption rate. Thus, immunization against determinants other than classical H‐2d (K, I, D, L) antigens (transmitted as a dominant character and different from Mls determinants) can elicit anti‐abortive effects. Furthermore, it was observed that the spleen cell endowed with the anti‐abortive effects was neither a T nor a B lymphocyte. In contrast, peritoneal cells were able to reproduce the phenomenon, indicating that it may be mediated by a cell of the macrophage‐monocyte lineage. Finally, a first gestation was substituted for allo‐immunization of CBA/J females. The anti‐abortive effects of a first pregnancy by BALB/c J males (and not by other H‐2k syngeneic or H‐2d allogeneic males) was observed in the course of a second pregnancy sired by DBA/2 J males. These data can be interpreted in terms of maternal recognition of an antigen present on both macrophages and trophoblast cells and necessary for a successful gestation, which is coded for by genes outside the K, I, D, L regions.
SIGNAL TRANSDUCTION VIA MHC CLASS II ANTIGENS ON B LYMPHOCYTES
Authors: Mooney N. , Hivroz C. , Ziai‐Talebian S. , Grillot‐Courvalin C. , Charron D.
Published: April 2007

The role of the MHC class II antigens in the activation of resting human B lymphocytes (B‐Go) was examined with respect to both early and late events in the activation process.

The (Ca2+)i induced by anti‐IgM was enhanced in the presence of, or following pre‐incubation with, an anti‐MHC class II DR antibody (D1.12). Pre‐incubation with a sepharose conjugated antibody (Seph.‐D1.12) augmented the proliferation of B‐Go in response to a sub‐optimal concentration of anti‐IgM.

The 2D PAGE profile of B‐Go differed from that of in vivo activated B lymphocytes. The 2D PAGE profile of B‐Go activated by Seph.‐D1.12 was not identical to the profile of B‐Go activated by either anti‐IgM or PMA.

These data suggest that the activation of B‐Go via the class II antigens shares part of the pathway of anti‐IgM induced activation but does not follow an identical pathway.
BIOLOGICAL SIGNIFICANCE OF BETA hCG, HLA AND OTHER MEMBRANE ANTIGEN EXPRESSION ON BLADDER TUMOURS AND THEIR RELATIONSHIP TO TUMOUR INFILTRATING LYMPHOCYTES (TIL)
Authors: Oliver R. T. D. , Nouri A. M. E. , Crosby D. , Iles R. L. , Navarette C. , Martin J. , Bodmer W. , Festenstein H.
Published: April 2007

Expression of beta human chorionic gonadotropin (βhCG) by bladder tumours has been shown to be associated with increased metastases and resistance to treatment with radiotherapy and chemotherapy. Preliminary results from typing frozen tumours using monoclonal antibodies against HLA determinants show reduced or lost expression of one or more antigens in two thirds of patients studied with a trend for more malignant behaviour and inability to generate tumour infiltrating lymphocyte expression using Interleukin‐2 in those patients whose tumours demonstrate loss. In this series βhCG expression was only seen in a subgroup of those demonstrating loss of HLA antigen expression. Studies of βhCG secreting bladder cancer cell lines showed that it was possible to induce class II HLA antigen expression with gamma Interferon, and that this treatment but not alpha Interferon reduced βhCG production by the cell line.
NOVEL HUMAN MHC CLASS I GENES ARE EXPRESSED BY TUMOUR CELL LINES REPRESENTING EMBRYONIC AND EXTRAEMBRYONIC TISSUES
Authors: Rinke de Wit T. F. , Vloemans A. A. , Van Den Elsen P. J. , Ward J. , Sutcliffe R. C. , Glazebrook J. , Haworth A. , Stern P. L.
Published: April 2007

The expression of HLA class I(‐like) genes was studied in two human developmental turnour cell lines representing embryonic (Tera‐2) and extra‐embryonic (Jeg‐3) origins. Neither cell line expresses polymorphic HLA‐A, ‐B, ‐C antigens as determined by standard serological typing. Tera‐2 cells express the HLA class I‐like T cell system A (TCA) determinants; Jeg‐3 cells are TCA negative. Northern blot analysis using an HLA class I α3 domain specific probe revealed markedly reduced levels of HLA class I(‐like) transcripts in both cell lines, which can be upregulated in Tera‐2 cells by incubation with gamma interferon (γIFN). Immunoprecipitation studies with a large panel of HLA class I/beta‐2 microglobulin (β2m) monoclonal antibodies (mAbs), detect low quantities of regular HLA class I heavy chains that are not associated with β2m on the surface of Tera‐2 cells. In contrast, Jeg‐3 cells express significant amounts of cell membrane β2m associated molecules of 41 and 45 kilodalton (kD). Screening of a Tera‐2 cDNA library, yielded 30 clones that hybridize to a full length HLA class I cDNA probe. Sixteen have been characterized and represent HLA class I sequences, consistent with the haplotype of Tera‐2. A similar screening of a Jeg‐3 cDNA library isolated clones representing a single novel HLA‐C‐like sequence; this probably codes for the 45 kD cell surface molecules of Jeg‐3. The 41 kD molecule may be encoded by the HLA‐6.0 gene since this is constitutively expressed in Jeg‐3 cells.
MHC CLASS I EXPRESSION ON HUMAN TUMOUR CELLS AND THEIR SUSCEPTIBILITY TO NK LYSIS
Authors: Pena J. , Solana R. , Alonso M. C. , Santamaria M. , Serrano R. , Ramirez R. , Carracedo J.
Published: April 2007

Although natural killer (NK) activity is not restricted by the major histocompati‐bility complex (MHC), it has been suggested that the level of expression of MHC antigens by target cells may influence their lysis by NK cells. We have studied the NK susceptibility of 20 cell lines obtained from primitive and metastatic human tumours and the K562 cell line treated with γ‐interferon, phorbol ester TPA and tumour factor NK‐RIF.

When the levels of MHC class I antigen expression on the human tumour cell lines and their NK susceptibility were compared, no relationship between these two parameters was observed. Futhermore the treatment of K562 with either γ‐interferon, TPA or NK‐RIF decreased its NK susceptibility independently of MHC class I expression.

These results indicate that the MHC class I antigen is not the only factor directly involved in NK susceptibility and suggest that other membrane structures modulated by γ‐interferon, TPA or NK‐RIF may also influence NK susceptibility.
SUSCEPTIBILITY EPITOPE ON HLA‐DR β CHAIN FOR RHEUMATOID ARTHRITIS AND THE EFFECT OF THE POSITIVITY ON THE CLINICAL FEATURES
Authors: Takeuchi F. , Matsuta K. , Watanabe Y. , Tokunaga K. , Juji T. , Miyamoto T.
Published: April 2007

A highly significant association of an amino acid sequence, ‘70Q71R72R73A74A’ located on the DRβ‐1 chain, with rheumatoid arthritis (RA) was confirmed in Japanese patients using polymerase chain reaction. The ‘70QRRA74A’ is the most plausible candidate of susceptibility epitope in Japanese RA patients. The patients carrying the sequence showed slightly higher but not significant familial incidence. The positivity of the ‘QRRAA’ showed no effect on the positivity of the rheumatoid factor, rheumatoid nodules, and extra‐articular signs. Also no significant differences in other clinical parameters (ESR, CRP, Hb, A/G) and age at onset were observed regarding the positivity. The risk that the ‘QRRAA’ positive subjects would suffer from RA was estimated to be about 1.3% which meant 7.2 times easier to get RA than those without ‘QRRAA’.
LINKAGE OF NEUTROPHIL RESPONSE TO A MUTAGEN GENE (Nrm‐1) TO THE AGOUTI LOCUS IN THE RAT
Authors: Stolc Viktor
Published: April 2007

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 × (BDIV × AC1)Fl 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‐Id 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 < 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.
GENETIC ANALYSIS OF LEISHMANIA MEXICANA INFECTION IN MICE: SINGLE GENE (Scl‐2) CONTROLLED PREDISPOSITION TO CUTANEOUS LESION DEVELOPMENT
Authors: Roberts M. , Alexander J. , Blackwell J. M.
Published: April 2007

Subcutaneous inoculation of Leishmania mexicana amastigotes into the shaven rumps of DBA/2 mice results in a unique ‘no lesion growth’ phenotype not observed in other mouse strains. Statistical analysis (Kolmogorov‐Smirnov and log likelihood tests) of lesion diameters in F1, F2 and backcross progeny from (C57BL/6 × DBA/2) matings indicate that segregation between lesion growth and no lesion growth phenotypes comes under single gene control. The gene has been designated Scl‐2 for susceptibility to cutaneous leishmaniasis locus 2. Preliminary mapping studies using 12 of the 26 BXD recombinant inbred mouse strains suggest a location for Scl‐2 near Xmmv‐8 on a region of mouse chromosome 4 showing homology with human 9p. The identification and mapping of this murine resistance gene could provide an important tool for genetic analysis of susceptibility and resistance to cutaneous leishmaniasis in man.
RABBIT MAJOR HISTOCOMPATIBILITY COMPLEX IV. EXPRESSION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II GENES
Authors: Spieker‐Polet H. , Sittisombut N. , Yam P.‐C. , Knight K. L.
Published: April 2007

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.
MOLECULAR ANALYSIS OF H‐2 CLASS I MOLECULES EXPRESSED ON THE UV‐INDUCED TUMOUR 1591
Authors: McKinney D. M. , McMillan M.
Published: April 2007

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‐2q and H‐2s haplotypes. A166 and A149 are very similar if not identical to Dq and Lq 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 Dd compared to Ld. In addition A216 possess an identical isoelectric point to that of the Ks 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.