bluuebunny/crossref_metadata_2025 huggingface dataset:
C4* A6BQO: A NEW C4 HAPLOTYPE
Authors: Skanes Verna , Larsen Bodil
Published: April 2007

A C4 haplotype containing C4*A6 without C4*B1 is described. It occurred in the MHC haplotype HLA‐AL, Cw5, Bw44, C2*1, BF*S, C4*A6BQO, DR3, GLO 2. This haplotype was observed in five of eight siblings, including the propositus who was in renal failure. The C4A6 was not haemolytically active and this new haplotype is therefore of particular interest since it is functionally equivalent to the rare C4‐deficient haplotype C4*AQOBQO.
ANTIGEN BINDING TO LYMPHOID CELLS FROM UNIMMUNIZED MICE
Authors: DeLuca D.
Published: April 2007

Neonatal spleen populations have been studied for antigen‐binding capacity in an attempt to determine if the frequency of double antigen‐binding cells changes as the population matures. Just after birth, the frequencies of total ABC, double ABC and Ig‐bearing cells were similar to the frequencies seen in the adult bone marrow. During the first week after birth, the proportion of total ABC and Ig‐bearing cells rose sharply so that by 8 days after birth, these cells were about half of adult levels. The proportion of total double ABC, after a brief rise at day 1, remained constant throughout the test period. Thus, the proportion of total ABC which are doubles gradually decreases with age. Sedimentation velocity studies indicate that double ABC's tend to co‐sediment with cells which require a period of maturation before they can respond to a thymus‐independent antigen in irradiated hosts. Single ABC, on the other hand, tend to co‐sediment with cells which are immediately responsive to antigen, or require a shorter maturational period before they become responsive to antigen. All of these data, taken together with our other work, suggest the possibility that multiple ABC are clonally‐derived lymphocyte populations which become more restricted in their antigen‐binding capacity as they mature.
GENETIC LIMITS OF THYMIC IMMUNOSUPPRESSION OF ANTI‐HAPTEN ANTIBODY PRODUCTION IN XENOPUS LAEVIS LAEVIS, THE SOUTH AFRICAN CLAWAD TOAD
Authors: Ruben L. N. , James Heidi S. , Clothier R. H. , Balls M.
Published: April 2007

Thymic immunosuppression in adult Xenopus laevis laevis, the South African clawed toad, is antigen‐dependent and antigen‐specific, but it is not genetically restricted. In this report, we show that combination in vitro with a thymus from an immunized Xenopus laevis laevis can suppress antibody production to a hapten from spleen fragments, if the spleen fragments are derived from a subspecies of Xenopus laevis or a species of Xenopus which shares the same diploid chromosome number (2N = 36). Some aspects of the evolution of thymic immunosuppression are considered in the light of these results.
AN INTERESTING MONOCLONAL ANTI‐N PRODUCED FOLLOWING IMMUNIZATION WITH HUMAN GROUP O, NN ERYTHROCYTES
Authors: Fletcher A. , Harbour C.
Published: April 2007

Spleen cells from Balb/c mice given multiple injections of intact human erythrocytes (group O, NN) were fused with NS1 myeloma cells. Culture fluids from the resulting hybrid cells were screened for agglutinating antibody against a panel of erythrocytes. One cell line, 2/23, secreted an IgM antibody which reacted more strongly with NN than with MM cells. Neuraminidase or papain treatment of erythrocytes abolished agglutination whereas trypsin treatment did not. Reactions with U‐erythrocytes of different MN phenotypes confirmed the anti‐N specificity of monoclonal antibody 2/23. This is the first report of monoclonal anti‐N stimulated by the immunization of mice with intact erythrocytes.
VARIATION IN H‐2 ANTIGEN EXPRESSION ON LYMPHOMYELOID CELLS IN SEMI‐ALLOGENEIC IRRADIATION CHIMERAS
Authors: O'Neill Helen, C. , Ashman R. B. , Gallagher P. F. , Woodhams C. E. , Blanden R. V.
Published: April 2007

Spleen cells from 30 individual murine irradiation chimeras of the type (P1 x P2)F1→ P1 were compared in a rosetting assay for H‐2K and H‐2D cell surface antigen expression with normal (P1 x P2)F1 hybrid controls. Eleven out of the 30 chimeras were in the normal range, but the other 19 differed from F1 controls by 4‐ to 100‐fold in endpoint titre for at least one H‐2K or H‐2D antigen. Every possible class of variation was found, i.e. up or down variation of H‐2K or H‐2D antigens of P1 or P2 type. This evidence, together with data from T6 chromosome marker experiments which also showed full reconstitution of lethally irradiated P1 recipients by (P1 x P2)F1 donor lymphomyloid stem cells, suggested that incomplete reconstitution was not the cause of H‐2 antigenic variation.

Low expression of P2 H‐2 antigens on spleen cells derived from (P1 x P2)F1→ P1 chimeras was investigated further. Fifteen lethally irradiated (P1 x P2)F1 recipients of bone marrow cells from two such chimeras were all of normal F1 H‐2 phenotype when tested 10‐12 weeks after reconstitution, thus excluding stable, low P2 H‐2‐expressing variant F1 stem cells as a cause of the phenomenon. If P1 recipients were hyperimmunized against P2 cells before lethal irradiation and reconstitution with (P1 x P2)F1 stem cells, there were significantly fewer Till‐McCulloch colonies in their spleens 10 days after reconstitution than in spleens of unimmunized controls. Also > 90% of immunized recients died by 6 weeks after stem cell injection but two survivors both showed very low levels of P2 H‐2K and H‐2D antigens. These results together with previously published evidence of anti‐P2 Tc cell activity and P2 skin graft rejection in (P1 x P2)F1→ P1 chimeras suggested that residual anti‐P2 immunological capability in lethally irradiated P1 recipients may be associated with low P2 H‐2 expression on their F1‐derived spleen cells, although the mechanism does not involve selection of stable, variant F1 stem cells. The mechanism(s) of other classes of variation in H‐2 expression in (P1 x P2)F1→ P1 chimeras were not investigated.
TWO UNLINKED GENETIC LOCI INTERACT TO CONTROL THE HUMAN IMMUNE RESPONSE TO TYPE III GROUP B STREPTOCOCCAL ANTIGEN
Authors: Pandey J. P. , Baker Carol J. , Kasper D. L. , Fudenberg H. H.
Published: April 2007

Serum samples were collected from 30 healthy adult Caucasian volunteers before and after immunization with native type III polysaccharide of group B streptococcus. Serum antibody to this polysaccharide was measured and sera were typed for several Gm and Km(1) allotypes. A significant interactive effect of Gm(23) and Km(1) was found on immune responsiveness to native type III group B streptococcus polysaccharide antigen.
EVIDENCE OF ONLY ONE H‐2D/L ‐ RELATED GLYCOPROTEIN IN H‐2dm1 MUTANT CELLS
Authors: Hunt Pamela , Burnside,and Stephen S. , Sears Duane W.
Published: April 2007

Analyses of the H‐2D/L‐related glycoproteins from dm1 mutant cell extracts by sequential immunoprecipitation, by SDS gel electrophoresis and by tryptic peptide mapping indicate that dm1 cells express only a single glycoprotein with H‐2D/L‐related determinants. In contrast to the four H‐2D/L‐related antigens identified for the parental d haplotype viz. H‐2Dd, H‐2Md, H‐2Ld and H‐2Rd, separate and distinguishable “H‐2Ddm1”, “H‐2Mdm1”, “H‐2Ldm1” and “H‐2Rdm1” glycoprotein counterparts are apparently lacking in the dm1 mutant haplotype. Only a single H‐2D/L‐related glycoprotein is identified in dm1 extracts by standard serological methods and this glycoprotein is designated H‐2D/Ldm1 because of its H‐2Dd/H‐2Ld hybrid characteristics, as recently shown by Burnside and colleagues (1984). Thus, the seemingly complex phenotype of the dm1 mutant appears to originate primarily from one molecule having properties of two (or more) molecules of the parental haplotype.
ELECTROPHORETIC ANALYSIS OF HLA‐DR2 MOLECULES ISOLATED FROM HLA‐Dw2 AND HLA‐Dw 12 CELL LINES
Authors: Takenouchi* T. , Kasahara M. , Ogasawara K. , Ikeda H. , Ishikawa N. , Hawkin S. , Wakisaka A. , Aizawa M.
Published: April 2007

To answer the question of whether or not polymorphism exists among HLA‐DR2 molecules derived from cells homozygous for HLA‐DR2, but expressing different HLA‐D specificities, HLA‐DR2 molecules were isolated from HLA‐Dw2 and HLA‐Dw12 homozygous cells using a monoclonal antibody operationally monospecific for HLA‐DR2, and were compared to each other by two‐dimensional gel eletrophoresis. No electrophoretically discernible polymorphism was found in either the heavy or the light chain subunits of the HLA‐DR2 molecules. These findings are in marked contrast with previous observations that each of the HLA‐DR4‐associated HLA‐D clusters expresses an electrophoretically distinct HLA‐DR4 light chain.
GENETIC DIFFERENCES BETWEEN TWO SUBSTRAINS OF NZB MICE *
Authors: Oikawa T. , Katoh H. , Shoji Y. , Esaki K. , Ishikawa M. , Yuhki N. , Kuzumaki N. , Tateno M. , Yoshiki T.
Published: April 2007

We have compared the NZB/BINJ (/NJ) and NZB/BlPt (/Pt) mouse substrains with respect to a number of immunological and biochemical polymorphisms. In agreement with earlier findings by other workers, we detected histocompatibility antigen difference(s) between the two substrains. Serological analysis indicated that /NJ and /Pt expressed the same allotypes of H‐2, Thy‐1 and Lyt‐1 antigens, while they differed for the Lyt‐2 antigen. Amongst 15 biochemical polymorphisms, which we assayed, /NJ and /Pt differed for four, namely Pep‐3, Mup‐1, Gpd‐1 and Hbb. In addition, the two NZB substrains differed for the Hc marker (haemolytic complement).
GENETICS OF THE RAT CT SYSTEM: ITS APPARENT COMPLEXITY IS A CONSEQUENCE OF CROSS‐REACTIVITY BETWEEN THE DISTINCT MHC CLASS I ANTIGENS RT1.C AND RT1.A
Authors: Stephenson S. P. , Morley R. C. , Butcher G. W.
Published: April 2007

The rat CT antigens are a system of medial histocompatibility antigens linked to RT1, the rat major histocompatibility complex (MHC). They have aroused interest firstly because, despite their extreme serological weakness, they are targets for ‘unrestricted’ cytotoxic T lymphocytes (CTL); and secondly because they have appeared to represent a complex genetic system in terms both of the number of genetic loci involved and the number of distinguishable antigenic specificities expressed. The CT system was originally defined by the reactions of LEW anti‐F344 (RT1l anti‐RT1lvl) secondary in vitro CTL. These CTL reacted strongly on DA(RT1avl) targets, but much more weakly on AUG or PVG (RT1c) targets. We have used the recently derived RT1 recombinant rat strains PVG.R19 (RT1.AavlIavlCc) and PVG.R20 (RT1.AcIcCavl) to investigate the genetic control of this system. Contrary to previous interpretations, the results are consistent with a model in which CT is a single locus, which maps to the RTI.C region. In addition, our results demonstrate that there is cross‐reactivity of anti‐RT1C CTLs on RT1A products, and we suggest that the earlier placement of a CT locus in the RT1.A region was probably incorrect and a consequence of this cross‐reactivity.
Gm ALLOTYPES IN IgA DEFICIENCY
Authors: HammarströM L. , Grubb R. , Smith C. I. E.
Published: April 2007

Gm phenotypes were examined in 90 Swedish IgA‐deficient (<0.05 g/litre of serum IgA) donors and 40 normal first and second degree relatives of six of these donors. The Glm1,2, G3m5 and Km1 frequency in the group of IgA‐deficient donors did not differ from that found in the normal population. Among the relatives, HLA and/or Gm identical normal sibs were observed. Anti‐IgA antibodies were present in 29 of the IgA‐deficient donors and anti‐IgG in seven. No association between the two was found. A statistically significant association between the Glm‐2 phenotype and the presence of anti‐Iga antibodies was observed. When subdivided according to HLA type, a non‐random distribution of Gm phenotypes was seen in HLA‐B8/DR3 positive individuals with anti‐IgA antibodies (HLA‐B8/DR3 being the haplotype associated with IgA deficiency). These data suggest an association between IgA deficiency, anti‐IgA and the studied Gm allotypes.
LONG‐TERM PASSIVE ENHANCEMENT OF ALLOGENEIC SKIN GRAFTS WITH MONOCLONAL ANTIBODIES
Authors: Hansen Ted H. , Koprak Samuel L. , Wormstall Eva‐Marie , Olson Beverly J. , Jackson Ronald D.
Published: April 2007

Monoclonal antibodies (mAb) to graft‐specific class I or class II major histocompatibility antigens were tested for their ability to enhance the survival of allogeneic skin transplants. Mutant mouse strains were grafted with wild type tissue to restrict the antigenic differences being recognized For allogeneic recognition of the class I antigen Ld, mutant BALB/c‐H‐2dm2 (dm2) mice were grafted with wild type BALB/cKh skin, and two dm2 anti‐BALB/cKh mAb, 23‐10‐1 and 30‐5‐7, were tested for their ability to enhance. The anti‐Ld antibody 23‐10‐1 (IgM) was found not to enhance the survival of BALB/c skin of dm2 mice. 30‐5‐7, however, an IgG2a antibody of indistinguishable specificity from 23‐10‐1, prolonged graft survival for approximately 5 days. For recognition of selected Iab determinants, mutant B6. C‐H‐2bm12 (bm12) mice were grafted with wild type B6/Kh skin, and mAb specific for the serological change(s) in bm12 were tested for their ability to enhance. The anti‐Iab antibody 25‐9‐17 (IgG2a) was found not to enhance B6 grafts on bm 12 mice. However, the enhancement seen with 25‐9‐17 using (C3H x bm12)F1 recipients was extraordinary, such that treated mice had a mean survival time three times that of the controls. Since 25‐9‐17 is of C3H origin, these results suggest that allotype (or possibly idiotype) compatibility is important in antibody enhancement. Another anti‐Iab antibody 28‐16‐8 (IgM), also of C3H origin, failed to enhance a B6 graft on (C3H x bm 12)F1 mice. These studies demonstrate, therefore, that mAb can be used to enhance skin grafts and that both isotype and allotype may be important parameters which influence the ability of an antibody to enhance.
IMMUNOGLOBULIN ALLOTYPES IN PATIENTS IN END‐STAGE RENAL FAILURE
Authors: Laundy G. J. , Bradley B. A.
Published: April 2007

In a population of 282 Caucasoid patients in end‐stage renal failure (ESRF) Gm and Km typing has confirmed a significant increase in the frequency of the Gm1,2,17;21 haplotype. This was confined to an increase in the number of heterozygous Gm(1, 2, 3, 17; 21, 5, 10, 13, 14) individuals. A concomitant decrease in the frequency of presumptive Gm(3, 5, 10, 13, 14) heterozygotes was also confirmed. Analysis of individual renal diseases revealed significant immunoglobulin allotype, phenotype and haplotype frequency deviations in those patients presenting with hypertension, glomerulonephritis or pyelonephritis. The allotype distribution in patients with physical abnormalities of the urinary‐genital tract, whether congenital or acquired, was normal.
FEMALE POPLITEAL LYMPH NODE RESPONSES TO H‐ Y ANTIGEN ON MALE THYMOCYTES IN MICE
Authors: Králová J. , Němec M.
Published: April 2007

C57BL/10 (abbreviation B10) female mice give a high primary popliteal lymph node (PLN) response to syngeneic male thymocytes. The PLN response to the H‐Y antigen is suppressed if B10 females are primed by an intraperitoneal injection of syngeneic male cells. Suppression of the response can be induced by priming with not only syngeneic B10 male thymocytes but also allogeneic thymocytes which share the H‐2D locus of the H‐2b haplotype with the responder (Db restriction). On the other hand, B10.D2, B10.A, and HTO female mice, giving a low primary PLN response to H‐Y, give high secondary PLN responses when primed intraperitoneally with syngeneic male thymocytes. A high secondary response can also be obtained by priming with allogeneic male thymocytes which share the K/i> end loci (K, Aβ, Aα, Eβ, and Eα) of the H‐2 complex with the responder. Apparently the male thymocytes used for priming must share class I (and possibly class II) H‐2 loci with the female recipients to enable the recognition of the H‐Y antigen and subsequent development of the genetically determined type (suppression or amplification) of the secondary PLN response.
AUGMENTATION OF THE ANTIBODY RESPONSE BY HAPTEN HELP
Authors: Leech S. H. , Bryan C. F. , Elston R. C.
Published: April 2007

The purpose of the present work was to characterize the immune response (Ir) genes that influence augmentation of the antibody response by help with the hapten azobenzene‐arsonate (ABA). Hapten help was measured as the augmentation in the plaque‐forming cell (PFC) response to bovine gamma gloulin (BGG) after priming mice with ABA conjugated to ovalbumin (OVA) and challenging subsequently with ABA‐BGG. The first approach involved inbred mouse strains that were matched for H‐2 but differed in their non‐H‐2 genetic backgrounds. B10.D2 mice were low responders even though they shared the H‐2d haplotype with BALB/c and DBA/2 mice, which were high responders. C57BL/10 mice were high responders even though they shared the H‐2b haplotype with C57BL/6, C3H.SW, and A.BY mice, all of which were strains that were low responders. The second approach was to identify any segregation of H‐2 woth the gene(s) encoding susceptibility to hapten help in the backcross generation. (BALB/c x C57BL/6) F1 hybrids were backcrossed to C57BL/6. The results showed no association with the major histocompatibility complex (MHC).
FAILURE TO DETECT ASSOCIATION OF ISOLATED CLEFT PALATE WITH HLA ANTIGENS
Authors: Pairitz G. , Erickson R. P. , Schultz J. , Sing C. F.
Published: April 2007

HLA antigen frequencies have been determined in 282 controls and in 33 individuals with isolated cleft palate or the related birth defect velopharyngeal incompetence. No association of particular HLA antigens with this birth defect was found. A previously reported association of HLA A2 with cleft palate, in males, was not confirmed.
HLA CLASS I AND CLASS II ANTIGEN ASSOCIATIONS IN ACUTE LEUKAEMIAS
Authors: Navarrete C. , Alonso A. , Awad J. , McCloskey D. , Ganesan T. S. , Amess J. , Lister T. A. , Festenstein H.
Published: April 2007

HLA‐A,B,C and DR antigen frequencies were determined in a group of 188 patients suffering from acute myeloid (AML) and acute lymphoid leukaemia (ALL). These antigen frequencies were compared with those obtained on a panel of normal individuals (n= 109) of the same ethnic origin. The significance of the differences in the antigen distribution and the strength of the associations between particular HLA antigens and the disease were then calculated. The resuks obtained show a decreased frequency of HLA‐Awl9 in the overall group of patients and the group of patients with ALL. In addition, the antigen frequency of the HLA‐B18 and DRS(DRw11) antigens was also decreased in the overall group of patients and in those patients with AML but not in the patients with ALL. The results suggest that the antigen Aw l9 may confer some degree of resistance to the development of ALL and that the HLA‐B18 and/or DR5 antigens may be resistance factors for the development of AML.
CHARACTERIZATION OF THE SYNGENEIC ANTI‐TUMOUR RESPONSE AGAINST THE GR9
Authors: Delgado C. , Garrido A. , Perez M. , Garrido M. L. , Algarra I. , Garrido F.
Published: April 2007

Isoantisera and syngeneic monoclonal antibodies have been produced against A7, a clone derived from a BALB/c methylcholanthrene‐induced tumour named GR9. The antigens defined by the isoantisera and mAbs are widely distributed in a large number of GR9 clones as well as in other tumour cell lines of different aetiology and origin. Two GR9 clones with marked differences in H‐2 expression and syngeneic in vivo growth (A7, which is H‐2d‐positive and highly immunogenic and B‐9, which is H‐2d‐negative and highly malignant) were selected to further analyse the presence or absence of the antigens recognized by the syngeneic anti‐tumour antibodies.

Immunoprecipitation data with two different isoantisera revealed a group of proteins with a molecular weight of M, 65‐70,000 present in both clones. Furthermore, immunoprecipitation with the A7‐1 mAb again showed a single M, 65K band present in A7 and B9 clones. We conclude that the marked differences observed in the syngeneic growth of the two clones are not due to differences in tumour associated antigens (TAA), defined by syngeneic antibodies, and emphasize the role that class I H‐2 antigens could play in tumour rejection.
REPRESSION OF CLASS I H‐2K,H‐2D ANTIGENS ON GR9 METHYLCHOLANTHRENE‐INDUCED TUMOUR CELL CLONES IS RELATED TO THE LEVEL OF DNA METHYLATION
Authors: Bonal F. J. , Pareja E. , Martin J. , Romero C. , Garrido F.
Published: April 2007

The correlation between gene expression and DNA methylation is well established. In the present study we examined DNA methylation as a potential regulatory mechanism of class I histocompatibility antigen expression. We selected for study two cell clones from the same mouse tumour (GR9). One of them is H‐2 class I‐positive (A7) and the other negative (B9). Using five enzymes and three different probes, no rearrangement or deletion was detected in the MHC class I genes of the negative clone compared with the positive one. These results do not provide an explanation for the differences observed in the expression of class I antigens in A7 (Kd, Dd positive) and B9 (Kd, Dd negative). We then studied the DNA methylation status in both clones by Southern blot analysis. Clear differences between the Kd, Dd positive and negative clones were detected. Furthermore, both Kd and Dd were clearly expressed after culturing the H‐2 class I negative clone with the demethylating agent 5‐azacytidine. These results suggest that the methylation of certain MHC cytoshes is a regulatory mechanism of H‐2 class I gene expression.
LOSS OF HLA‐A,B,C IN COLORECTAL CARCINOMA IS RELATED TO THE DEGREE OF DE‐DIFFERENTIATION
Authors: Momburg F. , Moller P. , Moldenhauer G. , Hämmerling G. J.
Published: April 2007

By means of immunoperoxidase staining of frozen sections 100 primary colorectal carcinomas and 19 metastases were studied for the expression of HLA‐A,B,C antigens. A substantial number of the tumours showed a deficient class I expression. The loss of HLA‐A,B,C correlated with the degree of de‐differentiation.
DIFFERENTIAL EXPRESSION OF HLA CLASS I AND II ANTIGENS IN PRIMARY AND METASTATIC MELANOMAS
Authors: Lopez Nevot M. A. , Garcia E. , Pareja E. , Bonal F. J. , Martin J. , Ruiz‐Cabello F. , Serrano S. , Garrido F.
Published: April 2007

Class I and II histocompatibility antigen expression was studied in cryostat sections of biopsy tissues from 15 patients diagnosed as suffering from malignant melanoma, using monoclonal antibodies against HLA class I and II mono‐morphic determinants and an indirect immunofluorescence technique. Class I antigens were detected in three of the four primary melanomas and in five of the eleven metastatic melanomas. Class II antigens were expressed only in metastatic melanomas, in three out of eleven cases.

Some tumour cell suspensions were obtained and short‐term cultures were established. Radiobinding and immunoprecipitation studies were carried out in two cases, named M6 and M8. The results were comparable to those obtained with direct immunofluorescence. We modulated the expression of class I and II HLA antigens with interferon in M6 when adapted to tissue culture. This melanoma was class I and II negative; after IFNγ treatment it became strongly positive for class I and II antigens. In addition we have demonstrated, using Southern blot analysis with the restriction enzymes PvuII and EcoRI, that the M6 melanoma does not have any detectable alterations in its class IIβ genes.
EXPRESSION AND SUSCEPTIBILITY TO MODULATION BY INTERFERONS OF HLA CLASS I AND II ANTIGENS ON MELANOMA CELLS. IMMUNOHISTOCHEMICAL ANALYSIS AND CLINICAL RELEVANCE
Authors: Ruiter D. J. , BRöcker E.‐B. , Ferrone S.
Published: April 2007

Immunohistochemical analysis for non‐polymorphic determinants of HLA class I or class II antigens has been greatly facilitated by the use of monoclonal antibodies. Studies on the distribution of these antigens in tumour lesions emphasize their role in the tumour‐host interaction and in tumour histo‐pathology, especially as additional markers in the assessment of prognosis of melanoma patients. Changes in the expression of HLA antigens on tumour cells in vitro as induced by γinterferon may also occur in vivo as a result of local production by the T lymphocytic infiltrate in tumours.
LOSS OF POLYMORPHIC RESTRICTION FRAGMENTS OF CLASS I AND CLASS II MHC GENES IN A MALIGNANT MELANOMA
Authors: Angelini G. , Fossati G. , Radice P. , Longo A. , Piccioli P. , Pierotti M. A. , Ferrara G. B. , Parmiani G.
Published: April 2007

DNAs from human malignant melanoma cells and autologous peripheral blood lymphocytes were evaluated by Southern blot analysis with probes for class I and II HLA genes. DNA of melanoma cells digested with PvuII, EcoRI and BglI and hybridized with a DRB probe showed a loss of several fragments when compared with DNA from lymphocytes. The same DNAs were not distinguishable when hybridized with a DQB probe. Analysis of melanoma and autologous lymphocyte DNAs from the same patient with a class I cDNA, after digestion with several endonucleases, revealed a further loss of fragments in melanoma cells. Comparison of restriction fragment patterns of melanoma and lymphocytes with those of homozygous, serologically‐typed cell lines indicated that melanoma cells have lost fragments diagnostic of DR2 and A1 antigens. A densitometric analysis of signals of several oncogenes in comparison with that of DR indicated that a duplication of the remaining DR allele had occurred in melanoma cells.
MOLECULAR DEFINITION OF RETROVIRUS‐INDUCED ANTIGENS RECOGNIZED BY TUMOUR‐SPECIFIC H‐2‐RESTRICTED CYTOLYTIC T LYMPHOCYTES
Authors: Plata F. , Langlade‐Demoyen P. , Abastado J.‐P. , Berbar T. , Kourilsky P.
Published: April 2007

The antigenic specificities of H‐2‐restricted, tumour‐specific cytolytic T lymphocytes (CTL) were studied at the molecular level using CTL from BALB.B and C57BL/6 (H‐2b) mice sensitized to an H‐2b Gross murine leukaemia virus (MuLV)‐induced tumour. Target cells were produced by the double trans‐fection of mouse L cells (H‐29 with the cloned H‐2Kb or H‐2P gene and retro‐viral DNA derived from a molecular clone of Akv MuLV (closely related to Gross MuLV). Doubly transfected L cells which express either H‐2Kb or H‐2Db antigen and retroviral antigens are lysed in a virus‐specific manner by Gross MuLV‐immune CTL. The existence of two independent Gross MuLV‐immune CTL subpopulations, one restricted by H‐2Kb and the other by H‐2Db, is thus confirmed. Gross MuLV‐immune CTL from both BALB.B and C57BL/6 mice killed L cells that express Akv MuLV gag gene products and H‐2Kb or H‐2Db antigen. In contrast, only CTL from C57BL/6 mice killed L cells that express Akv MuLV env gene products and H‐2Kb or H‐2Db. This indicates that specific recognition of MuLV‐induced antigens by CTL can be selective and varies according to the origin of the CTL.
SIMULTANEOUS RESPONSES TO TD, TI‐1 AND TI‐2 ANTIGENS ORIGINATE FROM BOTH SPECIFIC AND MULTIPOTENT PRECURSORS
Authors: Fevrier M. , Bleux C. , Bouvet J.‐P. , Couderc J. , Liacopoulos P.
Published: April 2007

The classification of antigens into TD, TI‐1 and TI‐2 varieties raises the question of whether responses to these antigens are produced by distinct or identical subpopulations of B cells. In the present study we have examined the extent of intraclonal specificity variation in the progeny of PFC appearing after stimulation with two unrelated antigens. Mouse lymphoid cells were stimulated with pairs of TD and TI antigens, PFC were individually cultured and daughter PFC examined for their specificity. In all combinations used, PFC responding to TD antigen engendered, after 48 h of culture, a high frequency of PFC daughters expressing one or the other antibody specificity, notwithstanding the specificity of parental PFC. However, PFC responding to TI antigens seemed less subject to variation in specificity, and PFC daughters engendered after a 48 h culture period were, in the majority, of the parental specificity. These results are analysed in relation to different subpopulations of B cells.
RELATIONSHIP BETWEEN DQα AND DQβ RFLP AND CELL SURFACE POLYMORPHISMS OF CLASS II HLA ANTIGENS
Authors: Cascino I. , Rosenshine S. , Turco E. , Marrari M. , Duquesnoy R. J. , Trucco M.
Published: April 2007

DQα and β DNA probes of the human major histocompatibility complex (MHC) were hybridized to restriction enzyme‐digested genomic DNA with the aim of establishing a correspondence between the polymorphisms recognized by classical serology and DNA restriction fragment length polymorphisms (RFLP). In DR homozygous human cell lines, three distinct PstI fragments were recognized by the DQα probe and four PstI fragments were recognized by the DQβ probe. Each fragment was associated with a different group of DR antigens. Three allelic forms of either DXα or β genes were identified, but none showed any strong association with DR or DQ. Family segregation analysis at the DNA level further confirmed the DR linkage of the DQ alleles in estimations of gene frequencies of different alleles of DQα, DQβ, DXα and DXβ. Evidence was presented that the DQα and DQβ allelic forms described at the DNA level correspond to polymorphic determinants at the cell surface which can be defined serologically or in cellular assays. Our data suggest that the HLA‐DQ subregion‐encoded alloantigens should be defined at the individual α and β chain levels.
ELECTROPHORETIC RESOLUTION OF TWO RAT CLASS I ALLOANTIGENS EXPRESSED ON (WF x F344)F1 LIVER CELLS IN PRIMARY CULTURE
Authors: Hunt J. M. , Buckley M. T. , Laishes B. A. , Butcher G. W. , Desai P. A.
Published: April 2007

Polyvalent alloantisera, prepared by reciprocal immunization of F344 (RT1lv1 haplotypes) and WF (RT1u haplotype) rats, as well as monoclonal antibodies, were used to immunoprecipitate class I alloantigens from detergent extracts of monolayer cultures of 35S‐methionine‐labelled liver cells. Two‐dimensional IEF/SDS‐PAGE gel analysis resolved the RT1.Alv1 and RT1.Au class I antigens expressed on the liver cells in culture.
THE EXPRESSION OF MURINE Qa REGION GENE PRODUCT(S) IN L CELL TRANSFORMANTS
Authors: Fernandez N. , Festenstein H. , Alonzo A. , Biro P. A. , Labeta M. , Carolan E. , Houlihan J. , Mellor A. , Flavell R.
Published: April 2007

The cosmid H3.5, containing genes mapping to the murine H‐2 Qa region, was used to transfect L cells by the calcium phosphate co‐precipitation method. The resultant transfected cells expressed a Qa‐like determinant as detected by an immune serum raised against the transfectant cells and Qa specific monoclonal antibodies. Two‐dimensional gel analysis revealed the expression of a class I‐like heavy chain with a similar molecular mass to the Qa2 antigens of the positive strain B10 and B10.A but with a different isoelectric point. The cosmid H3.5 spans 40 kb of DNA and contains at least one complete Qa region gene which encodes the Qa‐like determinant detected in this study.
GENES WITHIN THE MAJOR HISTOCOMPATIBILITY COMPLEX INFLUENCE THE RESPONSE TO AMPICILLIN THERAPY AND SEVERITY OF RELAPSE IN H‐2 CONGENIC, SUSCEPTIBLE Itys MICE INFECTED WITH VIRULENT SALMONELLA TYPHIMURIUM
Authors: Maskell D. J. , Hormaeche C. E.
Published: April 2007

Control by genes within H‐2 of natural resistance to fully virulent salmonellae in susceptible mice was studied by the typhoid relapse model. Susceptible (Itys), H‐2 congenic C57BL/10 (B10) lines were infected with a lethal dose of the virulent S. typhimurium C5 and rescued from death by ampicillin therapy, inducing a chronic infection. The response to therapy and its cessation, both early and late in the infection, varied in different strains. B10 (H‐Zb) and B10.D2 (H‐2d) responded less well to therapy, and were more prone to relapse on its removal, than B10.A (H‐2a) or B10.M (H‐2f) mice. This haplotype distribution is the same as that previously reported for H‐2 linked resistance and susceptibility of similar mice to salmonellae of low virulence. The results indicate that resistance to a virulent salmonella capable of causing natural infection is influenced by genes within the MHC.
HLA EXPRESSION ON HUMAN GERMINAL CELLS
Authors: Kurpisz M. , Fernandez N. , Witt M. , Kowalik I. , Szymczynski G. A. , Festenstein H.
Published: April 2007

Ejaculated human seminal plasma cells obtained from 46 healthy men and 48 infertile patients were tested for expression of HLA class I and II antigens by complement‐mediated cytotoxicity, cell‐binding radioimmunoassay (CB‐RIA), and an ELISA involving monoclonal antibodies (mAbs). In a group of healthy men tested for HLA expression on human spermatozoa, 4 of 46 were positive for class I and II HLA antigens. However, the results were negative in a second examination of the same donors, possibly on account of alterations with time in the expression of various subpopulations of cells which are antigen positive or antigen negative. In a group of infertile patients, we found positive expression of HLA class I and II antigens in 7 of 48 men. The samples contained immature and mature sperm but no contaminating leucocytes or epithelial cells.
THE ELY‐1 LOCUS CONTROLS A DI‐ALLELIC ALLOANTIGENIC SYSTEM ON EQUINE LYMPHOCYTES
Authors: Byrns G. , Crump A. L. , Lalonde G. , Bernoco D. , Antczak D. F.
Published: April 2007

The ELY‐I locus controls the expression of a polymorphic cell surface antigen of equine lymphocytes which was detected using antibodies generated by alloimmunization with peripheral blood lymphocytes. The ELY‐1 antigens were not detected on erythrocytes or platelets by absorption experiments. The two alleles, which have been designated ELY‐1.1 and ELY‐1.2, are expressed codominantly and appear to constitute a closed system at the population level. In family studies, the ELY‐1 antigens segregated as products of an autosomal locus not linked to the major histocompatibility complex (MHC) of the horse. In the complement mediated lymphocyte microcytotoxicity test, antisera to the ELY‐1 antigens selectively killed peripheral blood lymphocytes which did not express surface immunoglobulin. The ELY‐1 antigens may be useful markers for equine T cells when assayed in this fashion. Three alloantisera were used in immune precipitation of iodinated and solubilized cell surface proteins from peripheral blood lymphocytes. Electrophoresis of the precipitates in sodium dodecyl sulphate (SDS)‐polyacrylamide gels demonstrated strong bands in the Mr 180–190K range that were shared in the three different preparations. These results suggest that the ELY‐1 allospecificities are expressed on an equine equivalent of the murine T200 molecule.
SHORT CU MMUNICA TION: OCCURRENCE OF THE IMMUNOGLOBULIN HAPLOTYPES Gm1,17;23;21 AND Gm1,2,17;23;21 IN A SAMPLE OF AUSTRALIAN CAUCASIANS
Authors: Propert D. N. , Janardhana V.
Published: April 2007

Phenotypes positive for G2m(23) but negative for Glm(3) and G3m(5,10,11,13,14) are generally very infrequent in Caucasian populations. We recently Gm typed 372 Australian blood donors, predominantly of European descent, and found two Gm(1;23) and five Gm(1,2;23) individuals among them. This finding suggests that the haplotypes Gm1,17:23;21 and Gm1,2,17,23,21 may occur, in some European populations, with a frequency considerably higher than has been generally assumed.
STRAIN DIFFERENCES IN THE EXPRESSION OF THE EPA‐1‐RESTRICTING ELEMENT
Authors: Hadley G. A. , Snider M. E. , Steinmuller D.
Published: April 2007

Epa‐1‐specific cytotoxic T lymphocytes (CTL) lyse epidermal cells (EC) of different Epa‐1+H‐2k strains, such as AKR, CBA, C58, and RF, at different levels. We used an H‐2Kk‐specific monoclonal antibody (mAb) to test the hypothesis that this phenomenon is due to differences in the H‐2‐restricting element. Initially, we established the specificity of this mAb for the Epa‐1‐restricting element by demonstrating its capacity to inhibit the lysis of CBA EC by Epa‐1‐specific CTL. We then used it as the probe in a cellular radioimmunoassay to quantify the expression of the restricting element by EC of different H‐2k strains. We found that C58 and RF EC bound significantly less of the mAb than did CBA EC. Although AKR also bound less of the mAb than did CBA EC, the difference was not statistically significant. To examine the generality of this phenomenon, we quantified the expression of Kk antigens on spleen cells (SC) of the same four strains. We found that RF SC, but not AKR or C58 SC, bound significantly less of the Kk mAb than did CBA SC. Thus, the differential CTL lysis of Epa‐1+ EC of different strains probably reflects differences in expression of the H‐2‐restricting element rather than of the nominal antigen.
GENETIC STUDIES OF LOW‐ABUNDANCE HUMAN PLASMA PROTEINS: VII. HETEROGENEITY OF THE C1, SUBCOMPONENT OF THE FIRST COMPLEMENT COMPONENT
Authors: Kamboh M. I. , Ferrell R. E.
Published: April 2007

Charge‐based structural variation has been observed in the C1, subcomponent of the first complement component C1 after isoelectric focusing and immunoblot‐ting. One common and two uncommon autosomal co‐dominantly expressed alleles, designated ClS*1, ClS*2 and ClS*3, have been recognized at the ClS structural locus. The frequency of these alleles was 0·979, 0·016 and 0·005, respectively, in a U.S. white population. No variation at the ClS locus was observed in a U.S. black sample (n = 95).
THE Mls LOCUS: PAST, PRESENT AND FUTURE
Authors: Janeway C. A.
Published: April 2007

This issue of the Journal of Immunogenetics is devoted to the Mls locus. It comprises papers presented at a recent Howard Hughes Medical Institute workshop devoted to this subject. The papers cover many aspects of Mls locus genetics, biology and function. Bringing these papers together should make it easy for investigators interested in this area to catch up on the most recent developments, as well as to learn the history of the development of this field. There is a growing interest in the Mls locus, and much of the background information needed to understand current research efforts can be found in the papers published here.
Mls DETERMINANTS RECOGNIZED BY T CELLS
Authors: Abe R. , Hodes R. J.
Published: April 2007

The relationship among different minor lymphocyte stimulatory locus (Mis) determinants, Mlsa, Mlsb, Mlsc and Mlsd, remains unclear. Because of the high degree of cross‐reactivity between Mlsa and Mlsd determinants, the weak stimulatory capacity of Mlsc, and the generally non‐stimulatory nature of Mlsb, some investigators have recently suggested that Mis is composed of only a single expressed allele originally defined as the a andd alleles. In order to clarify the nature of Mls determinants, T cell clones positively selected for reactivity to the three stimulatory Mls determinants, Mlsa Mlsc and Mlsd, were generated and their specificities defined by extensive genetic studies. The response pattern of these Mls‐specific clones as well as the results of primary mixed lymphocyte responses indicated that: (i) Mlsa and Mlsc determinants recognized by T cells are distinct, demonstrating that polymorphism does exist within the Mls system; and (ii) Mlsd is not an independent Mls type since Mlsd determinants are composed of Mlsa and Mlsc determinants and anti‐Mlsd T cell responses are, in fact, the sum of anti‐Mlsa and anti‐Mlsc responses.
EVIDENCE FOR A HISTOCOMPATIBILITY LOCUS PROBABLY LINKED TO BUT DISTINCT FROM Mls AND H‐25
Authors: Berumen L. , Halle‐Pannenko O.
Published: April 2007

BALB/c (Mlsb) and BALB.D2‐Mlsa strains of mice, both H‐2d, are congenic and differ for the Mls locus (and linked genes) located on chromosome 1. The BALB.D2‐Mlsa strain was obtained by introducing the Mlsa allele of DBA/2 mice into BALB/c mice. In previous studies we showed that BALB.D2‐Mlsa recipients reject, relatively rapidly, all skin grafts from BALB/c donors. We and other groups have questioned whether the rejections observed were indeed due to the incompatibility for Mlsb products or for products of a histocompatibility (non‐H‐2) locus linked to, but distinct from, Mlsb. To answer this question, several hybrids carrying either Mlsa or Mlsb in various genetic contexts were grafted with skin from Mls‐compatible BALB/c or BALB.D2‐Mlsa donors; in the genetic combinations selected, any rejection which might occur would reflect the effects of a non‐Mls incompatibility between BALB/c and BALB.D2‐Mlsa strains. In certain of the donor‐recipient combinations studied, the skin grafts were tolerated for > 200 days, but a relatively rapid rejection of BALB/c skin grafts was observed in (B10.D2 × BALB.D2‐Mlsa)F1 and (B10.BR × BALB. D2‐Mlsa)F1 hybrid recipients. These results indicated that in addition to Mls, the BALB/c and BALB.D2‐Mlsa strains differ for at least one other non‐H‐2 histocompatibility locus. The possible involvement of H‐25 was then investigated. Indeed, disparity for H‐25, which maps on chromosome 1 close to Mls, can induce relatively rapid skin graft rejection. The H‐25 allele of the DBA/2 strain has not been defined: we considered, therefore, that BALB/c and DBA/2 could be disparate at the H‐25 locus, and that H‐25 (transmitted by DBA/2 to the BALB.D2‐Mlsa strain, together with the Mlsa allele) could be responsible for the skin graft rejection we observed. Our results showed, however, that DBA/2, BALB/c and BALB.D2‐Mlsa strains of mice all share the H‐25c allele; they therefore ruled out a role for H‐25 incompatibility in the skin graft rejections we observed, and indicated that these rejections are due to the effects of a yet undefined histocompatibility locus (locus ‘x’), probably linked to, but distinct from, the Mls locus. Further experiments showed that the histocompatibility effect of locus ‘x’ cumulates with that exhibited by Mlsb (or by a putative histocompatibility locus linked to Mlsb).
GENETIC RELATIONSHIPS OF Mlsa AMONG POLYMORPHIC LOCI ON DISTAL MOUSE CHROMOSOME 1
Authors: Seldin M. F. , Abe R. , Steinberg A. D. , Hodes R. J. , Morse H. C.
Published: April 2007

The segregation of Mlsa with respect to genes localized distally on mouse chromosome 1 was examined in two sets of recombinant inbred (RI) strains. In order to localize Mlsa, a linkage map based on analysis of both interspecific backcross mice and multiple sets of RI strains was utilized: (centromere) ‐ Ren‐1,2‐10 centimorgans (cM)‐At‐3‐8cM.‐Apo‐A2/Ly‐17‐2 cM‐Spna‐1‐4cM.‐Akp‐1‐(telomere). The Mlsa allele was mapped to a region that extended just centromeric of Ly‐17 (one crossover in 40 RI strains) to just telomeric of Spna‐1 (no crossover in 40 RI strains). The identification of multiple polymorphic loci in the region of Mlsa should allow precise gene localization and assist in efforts to clone this gene.
Mlsa DETERMINANTS: RELATIONSHIP TO Fcγ RECEPTOR AND TISSUE DISTRIBUTION
Authors: Molina I. J. , Huber B. T.
Published: April 2007

We have analysed the genetic relationship between Misa and FcγR in mice. Using the FcγR‐specific DNA probes, we were unable to detect a restriction fragment length polymorphism (RFLP) which is consistent in DNA derived from Mlsa strains and which differed from that of Mlsb strains, while we could see a polymorphism that distinguishes Ly17.1 from Ly17.2, alleles of the FcγR. These results strongly suggest that Mlsa is neither a product of the αFcγR nor of the βFcγR gene.

Furthermore, we have re‐examined the tissue distribution of Mlsa determinants using a major histocompatibility complex (MHC) class II antigen‐positive T‐cell tumour as well as a pure population of bone marrow derived macrophages of Mlsa genotype. Both these cell types were recognized to varying degrees by alloreactive cells; however, none of them expressed functionally detectable Mlsa determinants. We conclude from our studies that Mlsa is a highly stimulatory self peptide that is exclusively expressed in B cells.
A COMMENT ON H‐2‐RESTRICTED T CELL RECOGNITION OF Mls DETERMINANTS: A QUESTION OF PERSPECTIVE
Authors: Peck A. B.
Published: April 2007

Data presented here address the question of whether T lymphocyte recognition of Mis determinants is MHC restricted. Using isolated T cell blasts from primary MLCs involving H‐2‐identical, Mls‐disparate strain combinations as responding cell populations in secondary MLCs, and measuring their responses against fresh stimulating cells from different strains, has permitted the study of reactions towards Mis determinants in the presence of MHC antigenic differences. Results strongly suggest that recognition of Mlsc (Mls‐2 locus) determinants is H‐2 restricted. In contrast, there is still little evidence that the recognition of Mlsa (Mls‐1 locus) determinants is H‐2 restricted. Furthermore, data are also presented which refute the notion that different H‐2 haplotypes possess different abilities to present Mlsa determinants to responding T cells.
Mls DETERMINANTS AND ANTI‐Mls RECEPTORS
Authors: Webb S. R. , Okamoto A. , Sprent J.
Published: April 2007

We review evidence from this laboratory that T cell recognition of Mlsa determinants is not controlled solely by the α‐β T cell receptor (TcR) molecule. We propose a model in which Mlsa recognition reflects a receptor‐ligand interaction between two sets of complementary accessory molecules, one molecule (Mlsa) being expressed on B cells and the other (the anti‐Mlsa receptor) on T cells; this interaction augments recognition of self class II molecules by the TcR. The biological role of Mls molecules might be to facilitate physiological T‐B interaction.
SYNERGY BETWEEN STIMULATOR CELLS IN THE INDUCTION OF THE ANTI‐Mlsa RESPONSE
Authors: DeKruyff R. H. , Laning J. , Dorf M. E.
Published: April 2007

We have identified two types of clones responsive to Mls determinants. One type responded vigorously to purified B cells from mice bearing Mlsa‐stimulatory determinants. The other type, including clone Lyl‐N5, responded vigorously to unfractionated spleen cells, but failed to respond to B cells alone or to spleenadherent cells (SAC) alone from the Mlsa‐bearing mice. Synergy between two stimulator cell types, B cells and SAC, was required to induce the Mls response of clone Lyl‐N5. The failure of clone Lyl‐N5 to respond to Mlsa‐bearing B cells was reversed by the addition of SAC taken from mice bearing the Mlsb allele or the non‐stimulatory Mlsb allele. B cells were required to provide the Mlsa determinant.

The Mls response of clone Ly1‐N5 is restricted by class II determinants shared by the H‐2b, H‐2d and H‐2k haplotypes, but not the H‐2q haplotype. The optimal response of the clone was obtained by using B cells bearing both Mlsa and the permissive H‐2 alloantigen. However, complementation was also observed between B cells bearing Mlsa and the non‐permissive Iaq and SAC bearing the non‐stimulatory Mlsb, but a permissive la epitope, resulting in activation of the clone.

Clone Ly1‐N5 responds to Mlsa‐bearing B cells only in the presence of SAC. The SAC provide an undefined signal required for the proliferation of certain clones such as clone Ly1‐N5, which is not provided by normal B cells. In this report, we show that the AKTB‐lb B‐cell tumour line stimulates the proliferation of clone Ly1‐N5, in the absence of SAC, suggesting that the tumour line has acquired the capacity to provide this signal.
MULTIDIRECTIONAL INTERACTIONS IN AN Mls‐DISPARATE RESPONSE
Authors: Goldbach J. , Kirchner H. , Kölsch E.
Published: April 2007

The murine T cell clone E11, isolated from a primary H‐2k‐histocompatible, one‐way mixed lymphocyte culture of B10.BR anti‐C3H/Tif spleen cells, has been used to analyse multidirectional interactions in Mil‐disparate responses. Several events can be observed. There is proliferation of T cells upon stimulation by macrophages or B cells of Mls‐disparate stimulator cells. In addition, one finds induction of differentiation of B cells of stimulator strains. E11 T cells inhibit spreading and differentiation of macrophages of stimulator strains and also prevent the production of a T cell growth‐supporting mediator by Mls‐disparate spleen cells. All these phenomena can be explained by Mlsa,d,c‐specific induction of gamma‐interferon (γ‐IFN) production in the responder B10.BR (Mlsb) E11 T cells. It is suggested that γ‐IFN, as a regulator of feedback mechanisms, plays an essential role in Mls‐disparate cell interactions.