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P Parham

Publications and source records attributed to P Parham.

At least 235 records · Page 13Linked to original sources
PubMed1991

HLA class I nucleotide sequences, 1991.

The HLA class I sequences included in this compilation are taken from publications listed in the accompanying paper, Nomenclature for factors of the HLA system, 1990 (Bodmer et al., 1991), and also in Nomenclature for factors of the HLA system, 1989 (Bodmer et al., 1990). Where discrepancies have arisen between reported sequences the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments identity between residues is indicated by a hyphen (-). An unavailable sequence is indicated by a full point (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗
PubMed1991

Somatic cell mapping of bovine clathrin light chain genes: identification of a new bovine syntenic group.

Two bovine DNA probes (LCa and LCb) complementary to the clathrin light chain genes were hybridized to DNAs from bovine hamster hybrid somatic cell lines retaining different combinations of bovine chromosomes. Concordancy of retention of the clathrin genes was compared to existing syntenic data for the domestic cow. LCb identified a single locus. CLTB, concordant with the genes encoding bovine anti-Müllerian hormone (AMH) and bovine osteonectin from bovine syntenic group U22. LCa recognized two loci. CLTAL1 from a previously unidentified bovine syntenic group. U25, and CLTAL2 which is concordant with GGTB2, a gene marker for bovine syntenic group U18.

Animals↗
PubMed1991

HLA class I nucleotide sequences, 1991.

The HLA Class I sequences included in this compilation are taken from publications listed in the accompanying paper, Nomenclature for factors of the HLA system, 1990 and Nomenclature for factors of the HLA system, 1989. Where discrepancies have arisen between reported sequences the original authors have been contacted where possible, and necessary amendments to published sequences have been incorporated into this alignment. Future sequencing may identify errors in this list and we would welcome any evidence that helps to maintain the accuracy of this compilation. In the sequence alignments identity between residues is indicated by a hyphen (-). Unavailable sequence is indicated by a period (.). Gaps in the sequence are inserted to maintain the alignment between different alleles showing variation in amino acid number.

Base Sequence↗
PubMed1990

The calcium-binding site of clathrin light chains.

Clathrin light chains are calcium-binding proteins (Mooibroek, M. J., Michiel, D. F., and Wang, J. H. (1987) J. Biol. Chem. 262, 25-28) and clathrin assembly can be modulated by calcium in vitro. Thus, intracellular calcium may play a regulatory role in the function of clathrin-coated vesicles. The structural basis for calcium's influence on clathrin-mediated processes has been defined using recombinant deletion mutants and isolated fragments of the light chains. A single calcium-binding site, formed by residues 85-96, is present in both mammalian light chains (LCa and LCb) and in the single yeast light chain. This sequence has structural similarity to the calcium-binding EF-hand loops of calmodulin and related proteins. In mammalian light chains, the calcium-binding sequence is flanked by domains that regulate clathrin assembly and disassembly.

Amino Acid Sequence↗
PubMed1990

Uncoating protein (hsc70) binds a conformationally labile domain of clathrin light chain LCa to stimulate ATP hydrolysis.

Uncoating of clathrin-coated vesicles is mediated by the heat shock cognate protein, hsc70, and requires clathrin light chains (LCa and LCb) and ATP hydrolysis. We demonstrate that purified light chains and synthetic peptides derived from their sequences bind hsc70 to stimulate ATP hydrolysis. LCa is more effective than LCb in stimulating hsc70 ATPase and in inhibiting clathrin uncoating by hsc70. These differences correlate with high sequence divergence in the proline- and glycine-rich region (residues 47-71) that forms the hsc70 binding site. For LCa, but not LCb, this region undergoes reversible conformational changes upon perturbation of the ionic strength or the calcium ion concentration. Our results show that LCa is more important for interactions with hsc70 than is LCb and suggest a model in which the LCa conformation regulates coated vesicle uncoating.

Adenosine Triphosphatases↗
PubMed1990

Cytotoxic T cell recognition of an endogenous class I HLA peptide presented by a class II HLA molecule.

Human leukocytes were stimulated in vitro with peptides corresponding in sequence to the highly variable helix of the alpha 1 domain of various HLA-B and -C molecules. A CD4+ CD8- cytotoxic T cell line, CTL-AV, that is specific for the HLA-B7 peptide presented by HLA-DR11.1 was obtained. The HLA-DR11.2 molecule, which only differs at three residues from HLA-DR11.1, did not present the HLA-B7 peptide to CTL-AV. Peptides from the alpha 1 domain helix of other HLA-A and HLA-B molecules, but not HLA-C molecules, competed with the HLA-B7 peptide for binding to HLA-DR11.1. A cell line (WT50) that coexpresses HLA-B7 and HLA-DR11.1 was killed by CTL-AV in the absence of any added HLA-B7 peptide. The processing and presentation of HLA-B7 in these cells appears to be through the endogenous, and not the exogenous, pathway of antigen presentation. Thus, Brefeldin A inhibits presentation and chloroquine does not. Furthermore, introduction of purified HLA-B7 molecules into HLA-DR11.1+, HLA-B7- cells by cytoplasmic loading via osmotic lysis of pinosomes, but not by simple incubation, rendered them susceptible to CTL-AV killing. These results provide an example of class II major histocompatibility complex (MHC) presentation of a constitutively synthesized self protein that uses the endogenous pathway of antigen presentation. They also emphasize the capacity for presentation of MHC peptides by MHC molecules.

Anti-Bacterial Agents↗
PubMed1990

Apparent lack of MHC restriction in binding of class I HLA molecules to solid-phase peptides.

The specificity of binding of solubilized, purified HLA-A,B molecules to solid-phase peptides has been examined using the assay described by Bouillet et al. [1989. Nature (Lond.). 339:473.] 64 peptides derived from the sequences of viral antigens, HLA-A,B,C heavy chains, and clathrin light chains were tested for binding to HLA-A2.1, Aw68.1, Aw69, B44, and B5, molecules that differ by 5-17 residues of the peptide binding groove. 15 of the peptides, including those known to be T cell epitopes, gave significant binding. The pattern of peptide binding for each of the five HLA-A,B molecules was not significantly different. Binding was demonstrated to be a property of native beta 2m-associated HLA-A,B molecules that preserved conformational antigenic determinants after binding to peptide. In comparison to our previous results from solution-based assays the proportion of HLA-A,B molecules that can bind solid-phase peptides is very high. This accessibility of solid-phase peptides to the binding site of MHC molecules may be directly related to the observed absence of MHC specificity in the binding.

Amino Acid Sequence↗
PubMed1990

Recognition of an HLA public determinant (Bw4) by human allogeneic cytotoxic T lymphocytes.

The human class I HLA molecules are composed of both polymorphic, or private, and conserved, or public, regions. The private regions are recognized by alloreactive T cells and also serve as restriction elements for peptide presentation to autologous cells. Although the ability of public determinants to elicit antibody responses is well documented, little is known of their role in T cell function. In this study we examine the ability of one of these public HLA determinants, designated Bw4, to serve as a target Ag for CTL. We show that for some individuals the HLA-Bw4 epitope can function as a restriction element for CTL. This finding has important implications for organ transplantation.

Amino Acid Sequence↗
PubMed1990

A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2.

Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.

Antigens, CD↗
PubMed1990

HLA-AR, an inactivated antigen-presenting locus related to HLA-A. Implications for the evolution of the MHC.

The MHC contains many class I genes other than those known to present peptides to T lymphocytes. These additional class I genes vary between species and their functions are unknown. Genes involved in Ag presentation, HLA-A,B,C in humans, are highly diverse whereas other class I genes are of much more limited diversity. We have studied alleles of a gene, HLA-AR, that is closely linked and structurally related to HLA-A; properties consistent with these two loci having been formed by a gene duplication. Compared to HLA-A the diversity in HLA-AR is much less, and does not focus on residues of a putative Ag recognition site. However, the structure of HLA-AR alleles closely resembles those encoding Ag-presenting molecules, although the presence of one or two deleterious mutations prevents these alleles being active in Ag presentation. These results suggest HLA-AR derives from an Ag-presenting locus that became inactivated, possibly as a result of positive natural selection due to changing demands on T cell immunity. Thus absence of diversity may sometimes correlate with loss rather than preservation of function in class I MHC genes.

Alleles↗
PubMed1990

Conservation and diversity in families of coated vesicle adaptins.

The complete sequence of the beta adaptin subunit of the plasma membrane adaptor complex from coated vesicles has been elucidated. Complementary cDNA clones from human fibroblasts, rat lymphocytes, and bovine lymphocytes have been isolated, sequenced, and compared with each other and with beta adaptin sequences from rat brain (Kirchhausen, T., Nathanson, K.L., Matsui, W., Vaisberg, A., Chow, E.P., Burne, C., Keen, J.H., and Davis, A.E. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 2612-2616). Surprisingly, the 937-amino acid beta adaptin polypeptide is totally conserved between species. This remarkable homology contrasts with the absence of significant sequence similarity between the alpha (Robinson, M.S. (1989) J. Cell Biol. 108, 833-842) and beta adaptins of the plasma membrane adaptor complex. Diversity within each adaptin family is created by the expression of different genes and by tissue-specific differential splicing. The structures of the beta and alpha adaptins can both be divided into two globular domains interconnected by a variable and potentially flexible stalk domain.

Adaptor Protein Complex alpha Subunits↗
PubMed1990

Guilt by association: HLA-B27 and ankylosing spondylitis.

The remarkable association between HLA-B27 and ankylosing spondylitis (AS) remains an enigma. While previous reviews have discussed the controversies surrounding the involvement of bacteria in the etiology of this disease and the sequence variability between subtypes of HLA-B27, concepts of disease mechanism remain ill-defined. In this article Richard Benjamin and Peter Parham synthesize new data on the structure and function of HLA class I molecules into possible mechanisms that might underly the pathogenesis of AS.

Amino Acid Sequence↗
PubMed1990

Topographic map of the HLA-A2 CREG epitopes using human alloantibody probes.

The topographic architecture of the epitopes expressed on the HLA-A2 glycoprotein using murine monoclonal antibody (mAb) probes indicates at least two sterically distinct domains. Previously, we have demonstrated using human HLA alloantibodies (aAb) that multiple determinants are expressed on each HLA antigen: the highly polymorphic private epitopes and the public determinants that are shared within a family of crossreactive groups (CREG). Our objectives now focus on probing the antigenic structure of the HLA-A2-28-9-B17 CREG using highly specific aAb in conjunction with mAb that have previously been used for structural studies. Both mAb-mediated blockage of complement-dependent cytotoxic aAb and reciprocal antibody (Ab) binding inhibition assays with quantitation by fluorescence flow cytometry have been utilized. We have found that xenogeneic mAb directed against A2-69, A2-B17, and A2-28 crossblock aAb of the same serologic specificity, and vice versa, indicating that the epitopes they respectively recognize are at least in close steric proximity. However, additional HLA-A2, A28, and B17 aAb of private specificity and A2-28-9 aAb of public specificity, for which there are no known mAb counterparts, paint an additional complexity not previously known. We conclude that at least four different alloepitopes can be expressed by each serologically defined HLA antigen. Based on the primary sequence data, we have assigned the location and the amino acid substitutions which most likely account for these discrete epitopes. The unique private determinants are located on the alpha 1 domain together with the interlocus A2-B17 epitope while the public epitopes A2-69, A2-28-9 and A2-28 are located on the alpha 2 domain.

Antibodies, Monoclonal↗