Amino terminal sequence of heavy and light chains from ratfish immunoglobulin

The ratfish,Callorhinchus callorhinchus, a representative of the Holocephali, has a natural serum hemagglutinin (M _r 960 000), composed of heavy (M _r 71000), light (M _r 22 500), and J (M _r 16 000) chains. To approach the mechanisms that generate diversity at this level of evolution, the amino terminal sequence of the heavy and light chains was determined by automated microsequencing. The chains are unblocked and have modest internal sequence heterogeneity. The heavy chains show sequence similarity with the terminal region of the heavy chain from the horned shark,Heterodontus francisci, and other species. In contrast to the heavy chain, the ratfish light chains display low sequence similarity with their shark kappa counterparts. However, their similarity with the variable region of the chicken lambda light chains is about 75%.     

Simple high-performance liquid chromatographic purification procedure for porcine plasma haptoglobin

Haptoglobin is an acute-phase protein and its plasma levels increase consistently in response to infection and inflammation. Some evidence has demonstrated that haptoglobin is involved in the immune responses. In this study, we established a novel high-performance liquid chromatographic purification procedure for porcine plasma haptoglobin. The procedure required an ammonium sulfate fractionation and a HPLC Superose 12 gel-permeation chromatography. Purified porcine haptoglobin possessed one heavy (β) and light chain (α) on sodium dodecyl sulfate–polyacrylamide gel electrophoresis, under reducing conditions, with a M_r (molecular mass) of about 42 000 and 14 000 for heavy (β) and light chains (α), respectively. Although the N-terminal amino acid sequence of porcine heavy chain of haptoglobin has never been reported previously, the analyses of N-terminal amino acid sequence showed a great sequence similarity to that of human and other animal species. In addition, Western blot using our specific antibody prepared against porcine M_r 42 000 chain did react with human haptoglobin and likewise, the antibody against human haptoglobin also cross-reacted with purified porcine M_r 42 000 chain. Thus, it confirmed that the identity of the porcine protein purified from our procedures was as haptoglobin.     

Posttranslational Modifications and β/γ Chain Associations of Human Laminin α1 and Laminin α5 Chains: Purification of Laminin-3 from Placenta

Laminins assemble into trimers composed of α, β, and γ chains which posttranslationally are glycosylated and sometimes proteolytically cleaved. In the current paper we set out to characterize posttranslational modifications and the laminin isoforms formed by laminin α1 and α5 chains. Comparative pulse–chase experiments and deglycosylation studies in JAR cells established that the M_r 360,000 laminin α1 chain is glycosylated into a mature M_r 400,000 band while the M_r 370,000 laminin α5 chain is glycosylated into a M_r 390,000 form that upon secretion is further processed into a M_r 380,000 form. Hence, despite the shorter peptide length of α1 chain in comparison with the α5 chain, secreted α1 assumes a larger size in SDS–PAGE due to a higher degree of N-linked glycosylation and due to the lack of proteolytic processing. Immunoprecipitations and Western blotting of JAR laminins identified laminin α1 and laminin α5 chains in laminin-1 and laminin-10. In placenta laminin α1 chain (M_r 400,000) and laminin α5 chain (M_r 380,000/370,000 doublet) were found in laminin-1/-3 and laminin-10/-11. Immunohistochemically we could establish that the laminin α1 chain in placenta is deposited in the developing villous and trophoblast basement membrane, also found to contain laminin β2 chains. Surprisingly, a fraction of the laminin α1 chain from JAR cells and placenta could not be precipitated by antibodies to laminin β1–β3 chains, possibly pointing to an unexpected complexity in the chain composition of α1-containing laminin isoforms.     

A human homolog of the mouse CD8 molecule,Lyt-3: genomic sequence and expression

The CD8 antigen is a marker for those cytotoxic T cells that recognize antigen in the context of class I major histocompatibility antigens (MHC) and has now been identified in many species. In rodents the CD8 antigen is a heterodimer of two distinct chains, Lyt-2 and Lyt-3 in the mouse and OX-8 M _r 32 000 and 37 000 chains in the rat. Human CD8 has consistently been described as a homodimer/homomultimer on mature T cells made up of one chain homologous to the Lyt-2 and OX-8 M _r 32 000 chains. This paper identifies a human equivalent of the second rodent CD8 chain (Lyt-3 and OX-8 M _r 37 000 chains) at the genomic level and shows that this gene is transcribed in human thymocytes and in some acute leukemic T-cell lines. The existence of a human Lyt-3 homolog raises the possibility that human CD8, like mouse CD8, may exist as a heterodimer.     

Biochemical complexity of serum HLA class I molecules

Human serum was found to contain a variety of class I-like molecules by Western blotting with anti-class I heavy chain reagents: major bands usually are observed around M _r 44 000, 40 000, and 35 000–37 000. HLA-A24-positive individuals are distinguished by higher serum levels of M _r 44 000 and 40 000 class I-like molecules than those found in HLA-A24-negative individuals. The M _r 44 000 serum molecules are probably intact class I molecules that have been shed from the cell membrane, because they contain both a transmembrane segment (TM), as deduced from detergent-binding experiments, and a cytoplasmic tail (CT), as inferred from reactivity with an antipeptide serum specific for the cytoplasmic domain of class I antigens (RaCT). The M _r 35 000 and 37 000 molecules contain neither a TM nor a CT region and therefore are probably proteolytic breakdown products of cellular and/or serum M _r 44 000 molecules, although the existence of Q10-like molecules in man cannot be ruled out. The M _r 40 000 molecules do not contain a TM region. M _r 40 000 molecules reactive with the RaCT serum were found in the minority (2/13) of sera tested. We conclude that alternative splicing resulting in a precise excision of the TM exon plays a minor role in the generation of serum HLA class I antigens.Abbreviations used in this paper B2m beta-2 microglobulin - BSA bovine serum albumin - EBV-BLCL Epstein-Barr virus-transformed B lymphoblastoid cell line - mAb monoclonal antibody - SDS-PAGE sodium dodecyl sulfate-polyacrylamide gel electrophoresis - TCA trichloroacetic acid     

Human pre-α-inhibitor: isolation from a by-product of industrial scale plasma fractionation and structural analysis of its H3 heavy chain

Pre-α-inhibitor (PαI) is a serine proteinase inhibitor from human plasma. It comprises bikunin (BK) responsible for antiprotease activity, covalently linked to a heavy chain H3. Here we describe its isolation from a side fraction of an industrial preparation of plasma clotting factors. By using a highly specific polyclonal antiserum prepared from rabbit immunized with a H3P polypeptide obtained in a bacterial expression system, we were able to identify the fractions containing PαI. Then, taking advantage of the differential affinity of the members of the inter-α-inhibitor family (IαI) for heparin-Sepharose and blue-Sepharose, we isolated PαI. Its specific antitryptic activity was 580 IU/g, higher than that of IαI: 420 IU/g. Its M_r, determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, with or without prior reduction, was 130 000. Its peptide chains were identified by N-terminal sequencing. The H3 heavy chain was isolated from PαI by alkaline dissociation and anion-exchange chromatography. Its electrophoretic mobility was compared to that of the H1 and H2 heavy chains of IαI. In reducing conditions, it was quite similar to that of H2 (M_r 85 000) but clearly different from that of H1 (M_r 78 000). Thus, the so-determined apparent M_r of H3 was overestimated since its molecular mass determined by MALDI-TOF was 74 100. This result agrees with the proposed structure for H3. Indeed, by carbohydrate analysis and PNGase F digestion, we demonstrate that the two potential N-glycosylation sites present in the core-protein (theoretical mass: 69 454) are really occupied by two N-glycans, probably of biantennary type.     

Catfish Thrombocytes Express an Integrin-like CD41/CD61 Complex

A thrombocyte-specific antigen was identified in two closely related catfish,Ictalurus punctatusandIctalurus furcatus,by monoclonal antibodies 4-20 and 7-2. The antibodies immunoprecipitate two noncovalently associated glycoprotein chains ofM_r180,000 andM_r95,000. Under reducing conditions theM_r180,000 chain is resolved intoM_r150,000 and 32,000 subcomponents. Analysis of N-terminal amino acid sequences indicates homology of theM_r95,000 chain with the β₃integrin subunit and homology of theM_r150,000 chain with the α_IIbintegrin subunit. These antibodies induce catfish thrombocyte aggregation and alteration of cell shape. The data indicate conservation of the megakaryocyte/platelet-restricted CD41/CD61 complex in bony fish.     

Differential expression of laminin chains in hepatic lipocytes

The lipocyte is an important source of laminin in the normal liver. We have investigated the expression of the 3 chains of laminin in isolated rat lipocytes. Both B₁ and B₂ chains, but not A, were found in medium from 5-day-old lipocyte primary cultures by immunoblotting and immunoprecipitation of ³⁵S-labeled proteins after reducing SDS-polyacrylamide gel electrophoresis. An additional polypeptide of M_r=380 000 was identified by immunoprecipitation. Under non-reducing conditions only one M_r=900 000 band was revealed. High levels of B₁ and B₂ mRNAs were also demonstrated in 5-day-old cultured lipocytes while at the time of seeding, only B₂ chain mRNAs were clearly detectable. A chain mRNA was constantly absent. These results suggest that lipocytes produce a variant form of laminin in primary culture and that the M_r=380 000 polypeptide could be unrelated to the A chain of laminin.     

Crystal Structure,Cytotoxicity and Interaction with DNA of Zinc (II) Complexes with o-Vanillin Schiff Base Ligands

Two new zinc complexes, Zn(HL¹)₂ (1) and [Zn₂(H₂L²)(OAc)₂]₂ (2) [H₂L¹ = Schiff base derived from o-vanillin and (R)-(+)-2-amino-3-phenyl-1-propanol, H₃L² = Schiff base derived from o-vanillin and 2-amino-2-ethyl-1,3-propanediol], have been synthesized and characterized by single crystal X-ray diffraction, elemental analyses, TG analyses, solid fluorescence, IR, UV-Vis and circular dichroism spectra. The structural analysis shows that complex 1 has a right-handed double helical chain along the crystallographic b axis. A homochiral 3D supramolecular architecture has been further constructed by intermolecular C-H··· π, O-H···O and C-H···O interactions. Complex 2 includes two crystallographically independent binuclear zinc molecules. The two binuclear zinc molecules are isostructural. The 2-D sheet supramolecular structure was formed by intermolecular hydrogen bonding interaction. The fluorescence of ligands and complexes in DMF at room temperature are studied. The interactions of two complexes with calf thymus DNA (CT-DNA) are investigated using UV-Vis, CD and fluorescence spectroscopy. The results show that complex 1 exhibits higher interaction with CT-DNA than complex 2. In addition, in vitro cytotoxicity of the complexes towards four kinds of cancerous cell lines (A549, HeLa, HL-60 and K562) were assayed by the MTT method. Investigations on the structures indicated that the chirality and nuclearity of zinc complexes play an important role on cytotoxic activity.     

Identification and characterization of a mouse cell surface antigen with alternative molecular forms

We present the characterization of a new mouse cell surface protein, recognized by the 3138-specific monoclonal antibody. The expression of this antigen is predominantly restricted to the hematopoietic and lymphoid tissues: bone marrow, spleen, lymph node, and thymus. Immunoblot analyses show that the 3138 determinant is present on molecules with different apparent relative masses. The 3138 antigen migrates on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a single band of M _r 115 000 for normal nonstimulated spleen cells and thymocytes and as two bands of M _r 115 000 and M _r 125 000 for bone marrow cells and mitogen-stimulated spleen cells. The multiple sizes of the 3138 antigens (isoforms) found on various cell lines are not due to allelic polymorphism, but instead may reflect the specific cell type or reflect the cell's state of activation or maturation. Results from lectin chromatography and N-glycanase and neuraminidase studies suggest that the 3138 antigen is a heavily sialylated O-linked glycoprotein. The unusual features of this antigen indicate that it may be the mouse homologue of the rat W3/13 antigen and the human leukosialin/sialophorin antigens.Abbreviations used in this paper Con A concanavalin A - Gal galactose - Ga1Nac N-acetyl galactosamine - Ig immunoglobulin - IL-2 interleukin 2 - 2-ME 2-mercapto-ethanol - M _r relative mass - PAGE polyacrylamide gel electrophoresis - PMSF phenylmethylsulfonyl fluoride - SDS sodium dodecyl sulfate - Th T helper - TX-100 Triton X-100 - TTS 0.3% TX-100, 0.01 M Tris, pH 7.4, 0.15 M NaCl     

An acidic modification of the cytoplasmic domain contributes to the charge heterogeneity of the MHC class I antigens

 Polypeptide phosphorylation and sialylation of the glycan moieties contribute to the charge heterogeneity of the class I major histocompatibility complex glycoproteins. The present study demonstrates that a unique acidic modification unrelated to phosphorylation or glycosylation also affects the charge heterogeneity of the H2-K^k heavy chain of BW5147 lymphoma cells. In vitro cultivation of BW5147 cells results in changes in charge heterogeneity of the H2-K^k heavy chains due to the unique acidic modification. Sequential papain digestion of the 45 000 M _r H2-K^k glycoprotein yields a 42 500 M _r glycopolypeptide initially, followed by production of a 39 000 M _r glycopolypeptide. Results from experiments designed to localize and characterize the novel acidic modification suggest that the modification resides in the segment of the H2-K^k polypeptide located between the two papain cleavage sites. This portion of the polypeptide consists of the transmembrane region and part of the cytoplasmic domain of the H2-K^k heavy chain. At steady state, 25% of the total cell surface H2-K^k possesses this modification. In addition, the modification is mutually exclusive with the phosphorylation of the H2-K^k heavy chain at Ser-333. The possible biological significance of the novel modification of class I antigens is discussed. Received: 27 May 1997 / Revised: 10 September 1997     

Interactions of basement membrane components

The binding of laminin, type IV collagen, and heparan sulfate proteoglycan to each other was assessed. Laminin binds preferentially to native type IV (basement membrane) collagen over other collagens. A fragment of laminin (M_r 600 000) containing the three short chains (M_r 200 000) but lacking the long chain M_r 400 000) showed the same affinity for type IV collagen as the intact protein. The heparan sulfate proteoglycan binds well to laminin and to type IV collagen. These studies show that laminin, type IV collagen and heparan sulfate proteoglycan interact with each other. Such interactions in situ may determine the structure of basement membranes.     

Depolymerization of hyaluronan by sonication

High molecular weight hyaluronan (M _r 400 000) obtained from human umbilical cord was depolymerized by sonication for 10 h into small molecules and finally into molecules of constant size (M _r 11 000). The molecular size of the depolymerized hyaluronan was unaltered even under different conditions of sonication. After sonication, the main sugar residues at the reducing and non-reducing termini of depolymerized hyaluronan wereN-acetylglucosamine (86%) and glucuronic acid (98%), respectively. Hyaluronans derived from rooster comb (M _r 1×10⁶) andStreptococcus zooepidemicus (M _r 1.2×10⁶) were deploymerized into molecules of different but characteristic sizes by sonication. On the other hand, neither chondroitin sulfate nor glycogen was depolymerized by sonication. These results suggest that high molecular weight hyaluronan may have some weak linkages related toN-acetylglucosamine in the chain, which are extremely sensitive to sonication. At present, however, the nature of these linkages is still unclear.Abbreviations HA hyaluronan - PA 2-aminopyridine     

Glycosaminoglycan and DNA Binding Induced Intra‐ and Intermolecular Exciton Coupling of the bis‐4‐Aminoquinoline Surfen

Despite the diverse biological activities of the glycosaminoglycan (GAG) antagonist surfen, the molecular details of its interaction with biomacromolecules remain poorly understood. Therefore, heparin and DNA binding properties of surfen were studied by circular dichroism (CD) and UV absorption spectroscopy methods. High‐affinity (K_a ~ 10⁷ M^‐1) association of surfen to the chiral heparin chain gives rise to a characteristic biphasic CD pattern due to the conformational twist of the aminoquinoline moieties around the central urea bridge. At higher drug loading, intermolecular stacking of surfen molecules alters the induced CD profile and also provokes strong UV hypochromism. In contrast to the right‐handed heparin template, binding of surfen to the left‐helicity chondroitin sulfate chains produces inverted CD pattern. Large UV hypochromism as well as polyphasic induced ellipticity bands indicate that surfen intercalates between the base pairs of calf‐thymus DNA. Extensive CD spectroscopic changes observed at higher drug binding ratios refer to cooperative binding interactions between the intercalated drug molecules. The inherent conformational flexibility of surfen demonstrated here for the first time is important in its binding to distinct macromolecular targets and should be considered for rational drug design of novel GAG antagonists. Chirality 27:605–612, 2015. © 2015 Wiley Periodicals, Inc.     

Human non-lineage antigen,CD46 (HuLy-m5): purification and partial sequencing demonstrates structural homology with complement-regulating glycoproteins

CD46, until recently known as HuLy-m5, is a non-lineage restricted surface antigen ubiquitously expressed by almost all human cells except erythrocytes. The CD46 antigen is identified by the E4.3 monoclonal antibody (mAb) and exists at the surface of human peripheral blood lymphocytes (PBLs) as two acidic, non-disulfide bonded chains, and , ofM _r 66 000 and 56 000. Receptor density analysis showed that CD46 was of moderately low abundance on PBLs with 7.5×10³ molecules present on each cell. The two chains of CD46 were purified (144 000-fold) by immunoaffinity-chromatography with E4.3 mAb from the plasma membranes of a human spleen infiltrated with chronic myelogenous leukemia cells. Amino acid sequence analysis of the NH₂-terminal of both and chains yielded the same sequence; XEEPPQ/TFEAMELIGKPKPYYEIGE. Peptide mapping studies confirmed that both CD46 chains were closely related, except for one peptide fragment. This amino acid sequence is identical to that of the NH₂-terminal of the recently cloned membrane co-factor protein (MCP), a membrane protein that binds the C3b and C4b fragments of complement and acts as a co-factor for I protein-mediated decay of the complement convertases. CD46 shares a cross-reactive epitope with some primate retroviruses, and this may indicate that some retroviruses mimic the mechanisms used by autologous human cells to evade complement-mediated immune clearance. Offprint requests to: I. F. C. McKenzie.     

Karyophobic proteins : A category of abundant soluble proteins which accumulate in the cytoplasm

The cytoplasm of oocytes of Xenopus laevis is enriched in several soluble proteins which are either absent from the nucleus or are present there at very low concentrations. These molecules, collectively referred to as karyophobic (from the Greek verbs oβιν and oβλoθαi which are meant here in the sense of “to be afraid of” or “to avoid”) proteins represent more than 20% of the total soluble cytoplasmic proteins and include some of the most abundant soluble cellular components. They may be recovered from high-speed supernatant (S-100) fractions and, following sucrose gradient centrifugation, most of them appear in the form of complexes smaller than 8.5S. On denaturation in urea and two-dimensional gel electrophoresis these proteins appear to be comprised of polypeptides of widely different sizes (ca M_r 15 000–230 000) and isoelectric points covering a broad range of pH values (4.2–8.0). Gel filtration and isoelectric focusing of native karyophobic proteins show that the majority occur in acidic complexes smaller than M_r 150 000, including one case of a small karyophobic protein (C9; M_r 30 000). In contrast to karyophilic proteins and proteins equilibrating between nucleus and cytoplasm karyophobic soluble proteins from [³⁵S]methionine-labelled ooplasms, when injected into unlabelled oocytes, remain in the cytoplasm. Human proteins with a similar karyophobic behaviour have been identified in fractions of soluble proteins from HeLa cells; there, the major karyophobic protein (HCa, M_r 36 000) is also one of the most abundant soluble proteins.We conclude that the specific nucleocytoplasmic compartmentalization of soluble proteins is governed not only by the principles of exclusion of large molecules from nuclear uptake and the existence of karyophilic signals in certain proteins but that a series of soluble, globular proteins exist in the cytoplasm, which have other molecular features which selectively exclude them from distribution over the nucleus. The possible functional role of the selective enrichment of these abundant proteins, which so far have escaped attention, in establishing a cytoplasmic milieu is discussed.     

Isolation and partial characterization of nigrin b,a non-toxic novel type 2 ribosome-inactivating protein from the bark ofSambucus nigra L.

The bark ofSambucus nigra L. contains a non-toxic novel type 2 ribosome-inactivating protein that we named nigrin b.In vitro, nigrin b strongly inhibited mammalian protein synthesis but did not affect plant nor bacterial protein synthesis. The protein (M _r 58 000) contains two subunits, A (M _r 26 000) and B (M _r 32 000); linked by disulphide bridge(s). Nigrin b was found to be an rRNA N-glycosidase of the rRNA of intact mammalian ribosomes and shares a very good N-terminal amino-acid sequence homology with the anti-HIV-1 proteins TAP 29 and trichosanthin.     

Affinity labeling of high-affinity α-thrombin binding sites on the surface of hamster fibroblasts

The serine proteinase α-thrombin potently stimulates reinitiation of DNA synthesis in quiescent Chinese hamster fibroblasts (CCL39 line). ¹²⁵I-labeled α-thrombin binds rapidly and specifically to CCL39 cells with high affinity (K_d ≈ 4 nM). Binding at 37°C was found to remain stable for 6 h or more during which time no receptor down-regulation, ligand internalization and/or degradation could be detected. The structure of α-thrombin receptors on CCL39 cells was identified by covalently coupling ¹²⁵I-α-thrombin to intact cells using a homobifunctional cross-linking agent, ethylene glycol bis(succinimidyl succinate). By resolution in sodium dodecyl sulfate polyacrylamide gel electrophoresis we observed the specific labeling of a major α-thrombin-binding site of M_r ≈ 150 000 revealed as a ¹²⁵I-α-thrombin cross-linked complex of M_r ≈ 180 000. Independent of chemical cross-linking, ¹²⁵I-α-thrombin also formed a covalent complex with a minor, 35 000 M_r, membrane component identified as protease nexin. Two derivatives of α-thrombin modified at the active site are 1000-fold less than α-thrombin for mitogenicity. These two non-mitogenic derivatives bound to cells with similar affinity and maximal binding capacity as native α-thrombin, and affinity-labeled the receptor subunit of M_r 150 000. When present in large excess, during incubation of cells with α-thrombin, these binding antagonists were ineffective in blocking α-thrombin-induced DNA synthesis. These data suggest that the specific 150 000 M_r binding sites that display high affinity for α-thrombin do not mediate induction of the cellular mitogenic response.     

Purification of hepatic microsomal cytochromes P-450 from β-naphthoflavone-treated Atlantic cod (Gadus morhua), a marine teleost fish

Four isozymes of cytochrome P-450 were purified to varying degrees of homogeneity from liver microsomes of cod, a marine teleost fish. The cod were treated with β-naphthoflavone by intraperitoneal injection, and liver microsomes were prepared by calcium aggregation. After solubilization of cytochromes P-450 with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propansulfonate, chromatography on Phenyl-Sepharose CL-4B, and subsequently on DEAE-Sepharose, resulted in two cytochrome P-450 fractions. These were further resolved on hydroxyapatite into a total of four fractions containing different isozymes of cytochromes P-450. One fraction, designated cod cytochrome P-450c, was electrophoretically homogeneous, was recovered in the highest yield and constituted the major form of the isozymes. The relative molecular mass of this form (58 000) corresponds well with a protein band appearing in cod liver microsomes after treatment with β-naphthoflavone. Both cytochrome P-450c and a minor form called cytochrome P-450d (56 000) showed activity towards 7-ethoxyresorufin in a reconstituted system containing rat liver NADPH-cytochrome P-450 reductase and phospholipid. Differences between these two forms were observed in the rate and optimal pH for conversion of this substrate, and in optical properties. Rabbit antiserum to cod cytochrome P-450c did not show any cross-reactions with cod cytochrome P-450a (M_r 55 000) or cytochrome P-450d in Ouchterlony immunodiffusion, but gave a precipitin line of partial identify with cod cytochrome P-450b (M_r 54 000), possibly as a result of contaminating cytochrome P-450c in this fraction.     

Inherent Anti-amyloidogenic Activity of Human Immunoglobulin �� Heavy Chains

We have previously shown that a subpopulation of naturally occurring human IgGs were cross-reactive against conformational epitopes on pathologic aggregates of Aβ, a peptide that forms amyloid fibrils in the brains of patients with Alzheimer disease, inhibited amyloid fibril growth, and dissociated amyloid in vivo. Here, we describe similar anti-amyloidogenic activity that is a general property of free human Ig γ heavy chains. A γ₁ heavy chain, F1, had nanomolar binding to an amyloid fibril-related conformational epitope on synthetic oligomers and fibrils as well as on amyloid-laden tissue sections. F1 did not bind to native Aβ monomers, further indicating the conformational nature of its binding site. The inherent anti-amyloidogenic activity of Ig γ heavy chains was demonstrated by nanomolar amyloid fibril and oligomer binding by polyclonal and monoclonal human heavy chains that were isolated from inert or weakly reactive antibodies. Most importantly, the F1 heavy chain prevented in vitro fibril growth and reduced in vivo soluble Aβ oligomer-induced impairment of rodent hippocampal long term potentiation, a cellular mechanism of learning and memory. These findings demonstrate that free human Ig γ heavy chains comprise a novel class of molecules for developing potential therapeutics for Alzheimer disease and other amyloid disorders. Moreover, establishing the molecular basis for heavy chain-amyloidogenic conformer interactions should advance understanding on the types of interactions that these pathologic assemblies have with biological molecules.