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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helper T cells are triggered by molecular complexes of antigenic peptides and cell surface glycoproteins of the MHC (gene products of the major histocompatibility complex) on antigen-presenting cells. There is now a lot of evidence that the complexes between isolated class II MHC molecules and selected peptides have long half-lives of approximately one day. The reported equilibrium binding constants between antigenic peptides and class II MHC molecules however, are only micromolar, suggesting that the association rate constants are very low. The only reported association rate constant is for a chicken ovalbumin peptide (OVA323-339) binding to I-Ad, and is indeed remarkably low, about 1 litre per mole per second. Prompted by these unusual data, we have used the pigeon cytochrome-c peptide pCytc(88-104) and I-E reconstituted in planar lipid bilayers on glass slides to investigate further the kinetics of peptide-MHC reactions. We report the formation of two IEk-pCytc peptide complexes. One complex has slow apparent association and dissociation kinetics, very similar to those reported previously for the chicken ovalbumin peptide and I-Ad. The second complex forms and dissociates about a hundred times more rapidly. The short-lived complex shows peptide-MHC specificity and is a kinetic intermediate in the formation of the long-lived complex; the long-lived complex is recognized by specific T-helper cells.
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PMID:A kinetic intermediate in the reaction of an antigenic peptide and I-Ek. 253 41

The class II region of the major histocompatibility complex (Smh) in the mole rat, Spalax ehrenbergi, consists of only two gene families, P and Q, instead of the four families (P, O, Q, and R) found in all other mammals studied to date. The Spalax P family consists of at least four beta and three alpha genes or gene fragments. In DNA-hybridization experiments, two of the beta genes behave as bona fide P-family members in that they hybridize strongly with human DP beta probes and hybridize weakly with probes specific for other class II gene families. The other two beta genes, on the other hand, hybridize weakly with human DP beta probes and nearly as well with human DQ beta probes. To determine the evolutionary relationships among these P-like genes, we have sequenced one of them. The sequence reveals, on the basis of its organization, that the gene clearly belongs to the P family, yet, on the basis of its nucleotide sequence, it is only slightly more similar to human DP than to human DQ genes. These results indicate that in the Spalax the P family of genes split into two subfamilies, PA and PB. For unknown reasons, one of these subfamilies (PB) retained more similarity to the Q gene family than did the other (PA).
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PMID:Evolutionary diversification of class II P loci in the Mhc of the mole-rat Spalax ehrenbergi. 283 71

The major histocompatibility complex (Mhc) is a group of loci coding for lymphocyte membrane glycoproteins that provide the context for the recognition of foreign antigens in the initial phase of the immune response. The complex contains a large number of loci, some of which are highly polymorphic. The complexity and polymorphism pose a number of questions concerning the evolution of the Mhc. In an attempt to answer some of these questions, we have begun to study the Mhc of the mole-rat, Spalax ehrenbergi, a rodent representing a complex of sibling species occupying ecologically and geographically clearly delineated regions within the borders of Israel. In an earlier publication we identified the Spalax major histocompatibility (Smh) complex serologically and biochemically. Here, we analyze the Smh by Southern blotting of DNA fragments produced by restriction enzyme digestion. The fragments were hybridized to mouse probes specific for class I, class II, and C4 genes. The analysis has revealed that the Smh complex contains as many class I genes as the mouse does and that these genes are polymorphic. The number of class II genes could not be determined with certainty, but it is probably not greater than in the mouse. Polymorphism was also detected at the loci coding for the complement component 4 (C4), which are probably closely linked to the Smh complex. The polymorphism of mole-rat class I loci contrasts with the reported monomorphism of these loci in the Syrian hamster. Since the mole-rat leads a solitary, subterranean life, as the Syrian hamster does, ecology cannot be an explanation for the lack of class I polymorphism in the latter species.
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PMID:Major histocompatibility complex of the mole-rat. II. Restriction fragment polymorphism. 299 Nov 31

A genomic DNA library prepared from the kidney of the mole rat Spalax ehrenbergi was screened with mouse probes representing major histocompatibility complex genes that encode alpha and beta polypeptide chains of class II molecules (alpha and beta genes). Restriction maps were constructed for the cross-hybridizing clones, and the class II genes borne by these clones were identified. By this procedure, five main regions containing class II genes were established. One region contained four genes and two gene fragments, the second region contained two genes, the third region contained one gene and one gene fragment, and the remaining two regions contained one gene each. Altogether, six beta genes, two alpha genes, and three alpha-gene fragments were identified. Two of the genes (one alpha and one beta) were established as belonging to the DQ subclass, and all other genes were found to be members of the DP subclass. (Subclass designations are based on the human HLA class II genes). No genes belonging to the DR and DO (DZ) subclasses were found in the library. The absence of DR genes in S. ehrenbergi was also indicated when other experimental methods were used. At least some of the DP loci are polymorphic and most likely also functional. Thus, in the evolution of the mole rat, the DR (and probably also the DO) loci have been deleted and their function(s) has been taken over by the DP loci, which have expanded to a great extent. These findings argue for functional interchangeability of the individual subclasses of class II loci.
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PMID:Major histocompatibility complex gene organization in the mole rat Spalax ehrenbergi: evidence for transfer of function between class II genes. 303 9

The bicyclic anhydride of DTPA-1-14C (BADTPA-1-14C) was synthesized and reacted with an antibody to human melanoma associated antigen (MAA) and with one to human class II major histocompatibility complex antigen (HLA-DR). DTPA-1-C incorporation per mole of anti MAA at molar ratios of 1:1 to 200:1 ranged from 0.5 to 25, while immunoreactivity ranged from 49 to 9%. With antibody to HLA-DR, results were similar. Anti MAA, but not anti HLA-DR, demonstrated polymerization upon conjugation. BADTPA-1-14C provides a convenient and accurate method for measuring the amount of DTPA in monoclonal antibody preparations and its effect on immunoreactivity.
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PMID:A method for direct quantification of the amount of DTPA in 111In monoclonal antibody preparations. 304 Jun 33

Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.
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PMID:Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. 620 49

The mole-rat, Spalax ehrenbergi, is a complex subterranean rodent species whose habitat is restricted largely to the Middle East and North Africa. We typed over 50 mole-rats with mouse monoclonal and polyclonal antibodies specific for class I and class II major histocompatibility complex (Mhc) molecules. Some of these antibodies were produced against mouse Mhc molecules, others against Mhc molecules of other species. About 25% of the antibodies reacted with mole-rat lymphocytes in the cytotoxic test. Some of the serologically positive antibodies precipitated from a glycoprotein pool of mole-rat spleen cell molecules that corresponded in size with class I and class II molecules of other species. We conclude, therefore, that mole-rats, like other mammals, possess the Mhc which consists of class I and class II loci. We call this Mhc Spalax major histocompatibility (Smh) complex. The occurrence of a large number of different serotypes among the tested animals suggests that Smh loci are polymorphic. This Mhc polymorphism of the mole-rat contrasts with the monomorphism or oligomorphism of the Syrian hamster, a rodent with a similar ecology. Thus far no qualitative correlation could be found between Smh polymorphism and chromosome variation described in this superspecies.
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PMID:Major histocompatibility complex of the mole-rat. I. Serological and biochemical analysis. 638 77

MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is recognized by cytolytic T-cells. We have used a reverse transcription-polymerase chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from different types of tumors, melanomas from different stages of disease progression, normal diploid cell lines, and melanocyte and nevus tissue from which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue from all stages of disease, but not melanocytes, nevus tissue, or any normal diploid cell line tested. A fraction of tumor lines derived from various epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral blood cells from patients with melanoma. 5-Aza-2'-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines. At an optimum concentration of 1 microM DAC, MAGE-1 expression was detectable by 24 h, plateaued by 72 h, but remained high for two weeks after removal of DAC from treated 888-mel cells, consistent with induction by demethylation. With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC-treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility complex restricted cytolytic T-cell clone, whereas control untreated cells were not, suggesting that production of the antigen encoded by the MAGE-1 gene was induced by DAC and that it was presented in association with major histocompatibility complex class I molecules at the cell surface for T-cell recognition.
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PMID:Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine. 751 Oct 51

Cytotoxic T lymphocytes (CTL) recognize peptides in association with major histocompatibility complex (MHC) class I proteins, but how peptides bind to class I is not well understood. We used a fluorescence technique to measure antigenic peptide binding to a soluble, single-chain Kd (SC-Kd) molecule in which the Kd heavy chain was connected by a 15-residue link to beta 2-microglobulin. Peptides were covalently labeled at their N terminus with dansyl, and binding of dansylated Kd-restricted peptides to SC-Kd resulted in significant fluorescence enhancement, which could be inhibited by unmodified Kd-restricted peptides. Real-time binding of a dansylated peptide could be followed by monitoring the fluorescence at 530 nm. The dansylated Plasmodium berghei circumsporozoite (PbCS) 263-260 peptide bound to "empty" SC-Kd with an association rate constant of 1140 M-1s-1, and the subsequent spontaneous dissociation of the SC-Kd-peptide complex was slow. The dissociation increased dramatically after addition of excess unlabeled PbCS 253-260 peptide, but with a slower association constant for unlabeled peptide, 77 M-1s-1. Thus, the Kd-peptide complex on the surface of antigen-presenting cells should be stable, but high concentrations of peptides in the endoplasmic reticulum (ER) lumen would allow for peptide exchange on Kd before export to the surface. The apparent activation energy for PbCS 253-260 peptide binding to SC-Kd was 6.78 +/- 0.64 kcal/mole, similar to values previously reported for antigen-antibody interactions.
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PMID:Real-time measurement of antigenic peptide binding to empty and preloaded single-chain major histocompatibility complex class I molecules. 847 6

African mole-rats are a family of rodents exhibiting an eclectic range of social behaviour and occupying a variety of habitat types. These differences are likely to impact upon the risk of parasite transmission and virulence, with increasing sociality predicted to correspond to an increased risk of transmission. We investigate these factors by analysing the major histocompatibility complex (MHC), a set of genes responsible for encoding highly variable intermediaries of the vertebrate adaptive immune response. To this end we assessed selection at exons 2 and 3 of the MHC class II DQalpha1 gene of four African mole-rat species representing a range of social behaviours. We demonstrate that: (i) the overall pattern of selection at these exons differentiates according to the predicted function of different regions, with the presence of positive selection indicating the likely influence of host-parasite coevolution; and (ii) contrary to the often observed and predicted positive correspondence between sociality and the risk of parasite transmission, two highly social African mole-rat species in fact appear to have comparatively weak positive selection, suggesting diminished host immunity and thus a low overall risk of parasite transmission.
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PMID:Patterns of MHC selection in African mole-rats, family Bathyergidae: the effects of sociality and habitat. 1505 38


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