Differential expression of H-2Dd and H-2Ld histocompatibility antigens.

Weis, John H.; Murre, C

doi:10.1084/jem.161.2.356

Cited by 17 publications

(4 citation statements)

References 33 publications

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“…Although this conclusion assumes that RMA .S cells have defective transport of endogenous peptides, the precise lesion(s) in these cells has yet to be elucidated . Previous studies of the Ld class I molecule of the mouse suggest that it bears several unique features, including a weak avidity for 02m, a slower rate of intracellular transport, and a lower cell surface expression (31)(32)(33) . Furthermore, each of these deficiencies was found to be approximately threefold, suggesting they are interdependent .…”

Section: Discussionmentioning

confidence: 99%

The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure.

Lie

Myers

Connolly

et al. 1991

The Journal of Experimental Medicine

115

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SummaryTo better understand the biological implications of the association of ligand with major histocompatibility complex class I molecules, we have studied the Ld molecule of the mouse. The culturing of various nonselected cell lines with three different known Ld peptide ligands resulted in a two-to fourfold specific increase in surface Ld expression as detected by 10 of 11 different monoclonal antibodies (mAbs) recognizing Ld epitopes . These findings suggest that Ld molecules are not saturated with endogenous peptide ligands and thus have accessible binding sites . Exploiting this feature of Ld we demonstrate that the physical association of Ld with ligand is exquisitely specific, indicating that they function in determinant selection . In addition, a non-peptide-bound antigenic variant of Ld was specifically detected with an exceptional mAb designated 64-3-7. In comparison with other Ld molecules, 64-3-7+ Ld molecules are not peptide ligand inducible, are more susceptible to proteolysis, lack 02 microglobulin association, and display a slower rate of oligosaccharide maturation . In spite of their deficiencies, the non-ligandassociated 64-3-7 Ld molecules were detected on the surface of all cell types tested; however, they appear not to be recognized by alloreactive cytotoxic T lyphocytes .Class I MHC molecules are highly polymorphic 45-kD membrane glycoproteins that associate noncovalently with a-2 microglobulin (02m), 1 a non-MHC-encoded, non-membrane-bound 11-kD polypeptide . Although each MHC haplotype of the mouse contains approximately 40 class I genes, only a few have known functions . For example, the H-2d haplotype, represented in the BALB/c inbred strain, expresses three class I molecules designated Kd, Dd, and Ld that function as classical transplantation antigens. The K, D, and L molecules on virus-infected or allogeneic cells function as recognition structures for CTL . Crystallographic studies revealed that the highly polymorphic ul and cr2 domains of the class I molecule combine in an intricate folding pattern to form a single potential binding site (1-3) . In fact the putative ligand binding site of the crystallized class I molecules was found to contain heterogeneous material estimated to be til-2 kD. In other studies using functional assays, virusspecific CTL were found to recognize a processed virus-derived peptide ligand in the context of a self class I molecule (4) . There are now several examples where the specific virus-derived peptide has been identified for a given CTL clone (e .g., refer-'Abbreviations used in this paper. Ag, antigen ; 02m, /3-2 microglobulin ; BEA, brefeldin A . ences 5, 6). Furthermore, these peptide ligands have been found to be between 5 and 20 amino acids in length . Thus, there is complete concordance between the crystallographic and functional studies. In spite of this knowledge, direct evidence of the binding of peptide to class I molecules has been very difficult to demonstrate using in vitro binding assays analogous to ones previously used to show class II...

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Section: Discussionmentioning

confidence: 99%

The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure.

Lie

Myers

Connolly

et al. 1991

The Journal of Experimental Medicine

115

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“…Whereas differential regulation of HLA-A and -B is due to a small number of locus-specific differences in their ENH and IRE sequences, H-2K and H-2D loci have identical ENH and IRE sequences. In the case of mouse, however, the differential regulation of H-2 class I antigens appears to be controlled at the posttranslational level (60 …”

Section: Discussionmentioning

confidence: 99%

Transcriptional regulation of HLA-A and -B: differential binding of members of the Rel and IRF families of transcription factors.

Girdlestone

Isamat

Gewert

et al. 1993

Proc. Natl. Acad. Sci. U.S.A.

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HLA-A and -B transplantation antigens can be expressed differentiafly at the basal level and in response to interferons (IFNs). To determine which DNA control elements and nuclear factors are responsible for these differences,HLA-A and -B upstream regulatory regions were used in expression and mobility-shift analyses. The HLA-A enhancer was found to contain two Rel (KBF/NF-#cB) binding motifs, while the HLA-B enhancer has only one and is transactivated less well by overexpression of the NF-#cB p65 subunit. transcription (13, 14). Overexpression of IRF-1 has been shown to increase the basal and IFN-induced levels of class I expression (15, 16).HLA-A and -B genes are highly homologous but exhibit locus-specific differences in both their transcribed (17) andThe publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.upstream regions (18,19) and are not tightly coordinated in their regulation. They can differ in basal and induced levels of expression, with cortical thymocytes and related thymomas such as MOLT-4, for example, expressing low levels of HLA-A but undetectable , while HLA-B loci respond more strongly to IFNs (21,22) and are subject to stronger suppression by c-myc expression (23). We report here that some of the locus-specific differences between the ENH and IRE of HLA-A and -B have significant effects on the binding of the Rel and IRF families of transcription factors and consequently on the regulation of the two loci. MATERIALS AND METHODSCell Culture, Transfection, and Chloramphenicol Acetyltransferase (CAT) Assays. MOLT4 and YHHH (24) cell lines were maintained in Dulbecco's modified Eagle's medium, and JM and Daudi in RPMI 1640 medium, all with 5% fetal bovine serum. Induction of NF-KB in JM cells was achieved by a 2-hr treatment with phytohemagglutinin (PHA, 5 ,ug/ml; Sigma) and phorbol 12,13-dibutyrate (PBt2, 50 nM; Sigma). Transfections and CAT assays were performed as described (25). Cells were harvested 20 hr after transfection. IFN-aA (kindly provided by M. Brunda, Hoffmann-La Roche) was added after transfection at 2000 units/ml where indicated.Plasmids. CAT reporters were produced by cloning synthetic oligonucleotides into an Sph I site introduced into the Bgl II site at the 5' end of the metallothionein promoter of pMCAT3 (26) and verified by double-stranded sequencing. The Rel p50 and p65 expression plasmids (27) were kindly provided by A. Baldwin (University of North Carolina, Chapel Hill) and the CMV-GalVP16 vector (28) by P. O'Hare (Marie Curie Research Institute, Oxted, Surrey, U.K.).Electrophoretic Mobility-Shift Assays. Nuclear extracts from cell lines were prepared (29) and mobility-shift assays were performed (25) as described. Baculovirus Expression of IRF-1 and IRF-2. Human IRF-1 and IRF-2 clones were obtained from the lymphoid lines HUT78 and MOLT-4, respectively, by two rounds of amplification by polymerase chain reaction...

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“…A number of mechanisms could contribute to this variation in induction of CTL between the two epitopes, which are synthesized in vivo in identical cells in equimolar amounts. Firstly, these epitopes are presented by two different H-2 d molecules which may differ in their biochemical and biological properties (Weis & Murre, 1985). Secondly, the efficiency of processing of some, but not other peptides from polyepitope proteins can be affected by their flanking amino acid residues Oldstone et al, 1993 ;Rabinovich et al, 1994 ;Ria et al, 1990 ;Thomson et al, 1995 ;Whitton et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

Hanke

Blanchard

Schneider

et al. 1998

Journal of General Virology

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A vaccine against human immunodeficiency virus (HIV) is still awaited. Although the correlates of protection remain elusive, it is likely that CD8 M T cells play an important role in the control of this infection. To firmly establish the importance of these cells in protective immunity, a means of efficient elicitation of CD8 M T cell responses in the absence of antibody is needed and, when available, might represent a crucial step towards a protective vaccine. Here, a novel vaccine candidate was constructed as a multi-cytotoxic T lymphocyte (CTL) epitope gene delivered and expressed using modified vaccinia virus Ankara (MVA). The immunogen consists of 20 human, one murine and three rhesus macaque epitopes. The non-human epitopes were

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Differential expression of H-2Dd and H-2Ld histocompatibility antigens.

Cited by 17 publications

References 33 publications

The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure.

The specific binding of peptide ligand to Ld class I major histocompatibility complex molecules determines their antigenic structure.

Transcriptional regulation of HLA-A and -B: differential binding of members of the Rel and IRF families of transcription factors.

Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice.

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