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PubMed1991

Analysis of type II collagen reactive T cells in the mouse. II. Different localization of immunodominant T cell epitopes on heterologous and autologous type II collagen.

The specificity of the recognition of type II collagen (CII) by T cells in the DBA/l mouse was analysed using fragments of chick and rat CII obtained by cyanogen bromide (CB) cleavage. Firstly, DBA/l mice were immunized with chick CB fragments 5, 8, 9, 10, 11 and 12. Ten days later the draining lymph node cells were cultured with rat and mouse CII and the proliferative response was determined by incorporation of [3H]thymidine. All peptides were capable of triggering T cells recognizing rat CII but only CB9 immunized mice responded well to mouse CII. Secondly, lymph node cells from DBA/l mice immunized with rat and mouse CII were cultured with the CB fragments, including rat CB10 and CB11, and the proliferative response was determined. After immunization with rat CII, the response was strongly dominated by T cells recognizing CB11 with equal responses against chick and rat CB11. After immunization with mouse CII only rat CB10 gave a strong response. It is concluded that several epitopes on the CII molecule can be recognized by T cells in the DBA/l mouse and that most of these epitopes are shared by rat and chick CII but not mouse CII. These epitopes exhibit strong immunodominance. In mice immunized with intact heterologous CII, the immunodominant response is directed against one or more epitopes on the CB11 fragment present on several heterologous CII but apparently not on mouse CII. In mice immunized with autologous CII the immunodominant response is directed against one or more epitopes on the CB10 fragment, present on rat and mouse CII. They are either absent in chick CII or located in the carboxyterminal end of the CB10 fragment where a cyanogen bromide cleavage site is present in chick CII but not in rat CII. These results suggest that the proposed importance of CB11 in collagen-induced arthritis is due to activation of T cells reactive with heterologous CII only. These cells may be important for the induction of the strong auto-antibody-response after immunization with heterologous CII. Structures of importance for direct T cell involvement in the arthritic process and recognized by autoreactive T cells are suggested to be found on CB10.

Animals↗
PubMed1990

Arthritis in DBA/1 mice induced with passively transferred type II collagen immune serum. Immunohistopathology and serum levels of anti-type II collagen auto-antibodies.

Arthritis was induced in DBA/1 mice by passive transfer of syngeneic anti-type II collagen (CII) serum concentrate. After transfer of serum containing 0.2 or 0.5 mg anti-CII auto-antibodies the first clinical signs of arthritis appeared 48 h after injection. Severe clinical arthritis was detected 96 h after injection. Immunohistochemical analyses of joints 48 h after serum injection revealed synovial foci in intercarpal and metacarpophalangeal joints of macrophage-like cells, expressing C3bi-receptors and major histocompatibility complex class II molecules, and infiltration of few CD4+ lymphocytes. Later (96 h after injection), the inflamed synovia were dominated by C3bi-receptor+ polymorphonuclear cells. In contrast to conventionally induced collagen arthritis (CIA), the inflammatory infiltrates, filling joint spaces and synovial tissue, were extensively dominated by polymorphonuclear cells, whereas macrophage-like cells expressing class II molecules and a few T cells were seen only in the periphery of the developing pannus. The anti-CII serum induced arthritis may be used as a model for studies of humoral mediated mechanisms operating in conventionally induced CIA as well as in rheumatoid arthritis.

Animals↗
PubMed2003

Determination of the complete cDNA sequence of rat type II collagen and evaluation of distinct expression patterns of types IIA and IIB procollagen mRNAs during fracture repair in rats.

Elucidating the molecular mechanisms that underlie fracture healing is crucial to understanding and devising strategies for the management of fractures, especially those associated with a pathological condition such as diabetes or old age. Cartilage formation, and therefore the expression of type II collagen by chondrocytes, is a critical step in frac-ture healing. Two forms of type II collagen, IIA and IIB, are known to be produced by alternative splicing of the Alpha(1) (II) procollagen gene. We have followed the patterns of expression of these two forms of type II collagen to determine the nature of chondrocyte recruitment during fracture healing. First, we sequenced the rat collagen type II cDNA to design the primers. Second, using a competitive quantitative reverse transcription-mediated polymerase chain reaction, we provide evidence that (1) there is a basal level of type IIA collagen expression during the early stages of fracture healing; (2) transient but sharp up-regulation of IIA expression occurs concomitant with chondrogenesis and endochondral ossification; and (3) type IIB collagen is the predominant mRNA variant expressed at virtually all times during fracture repair.

Animals↗
PubMed2000

Comparison of the degradation of type II collagen and proteoglycan in nasal and articular cartilages induced by interleukin-1 and the selective inhibition of type II collagen cleavage by collagenase.

OBJECTIVE: To compare interleukin-1alpha (IL-1alpha)-induced degradation of nasal and articular cartilages in terms of proteoglycan loss and type II collagen cleavage, denaturation, and release; to examine the temporal relationship of these changes; and to investigate the effects of an inhibitor of collagenase 2 and collagenase 3 on these catabolic processes. METHODS: Discs of mature bovine nasal and articular cartilages were cultured with or without human IL-1alpha (5 ng/ml) with or without RS102,481, a selective synthetic inhibitor of collagenase 2 and collagenase 3 (matrix metalloproteinase 8 [MMP-8] and MMP-13, respectively) but not of collagenase 1 (MMP-1). Immunoassays were used to measure collagenase-generated type II collagen cleavage neoepitope (antibody COL2-3/4C(short)) and denaturation (antibody COL2-3/4m), as well as total type II collagen content (antibody COL2-3/4m) in articular cartilage and culture media. A colorimetric assay was used to measure total proteoglycan concentration (principally of aggrecan) as sulfated glycosaminoglycans (sGAG). RESULTS: IL-1alpha initially induced a decrease in tissue proteoglycan content in nasal cartilage. A progressive loss of proteoglycan was noted during culture in articular cartilages, irrespective of the presence of IL-1alpha. In both cartilages, proteoglycan loss was followed by IL-1alpha-induced cleavage of type II collagen by collagenase, which was often reflected by increased denaturation. The inhibitor RS102,481 had no clear effect on the reduction in proteoglycan content (measured by sGAG) and collagen denaturation in either cartilage, but at 10 nM it inhibited the enhanced cleavage of type II collagen, partially in nasal cartilage and completely in articular cartilage. CONCLUSION: IL-1alpha-induced cleavage and denaturation of type II collagen is observed in both hyaline cartilages and is secondary to proteoglycan loss. It probably involves different collagenases, since there is no evidence of a rate-limiting role for collagenase 1 in articular cartilage, unlike the case for nasal cartilage. Inhibitors of this kind may be of value in the treatment of cartilage damage in arthritis. Also, the ability to detect the release of type II collagen collagenase-generated fragments from degraded cartilage offers the potential to monitor cartilage collagen damage and its control in vivo.

Animals↗
PubMed1999

Mice lacking matrilin-1 (cartilage matrix protein) have alterations in type II collagen fibrillogenesis and fibril organization.

Matrilin-1 (cartilage matrix protein) is a homotrimeric protein that forms collagen-dependent and collagen-independent fibrils in the extracellular matrix of cartilage. In the growth plate of developing long bones, the gene for matrilin-1 is transcribed exclusively by the chondrocytes of the zone of maturation which is situated between the zones of proliferation and hypertrophy. When associated with the cartilage collagen fibril, which consists of collagens type II, IX, and XI, matrilin-1 displays a periodicity of 59.3 nm. Matrilin-1 also interacts with the proteoglycan, aggrecan. Because of its association with the collagen fibril, we tested the hypothesis that matrilin-1 may play a role in collagen fibril formation and cartilage matrix assembly by generating mice with targeted mutations in the matrilin-1 gene. Ultrastructural studies of the cartilage of growth plates of matrilin-1 null mice reveal an abnormal type II collagen fibrillogenesis and fibril organization in the matrix of the zone of maturation. These results represent the first report on the regulation of the heterotypic type II collagen fibril by a non-collagenous protein. The abnormal fibrillogenesis had no obvious effects on skeletal development, on the organization of chondrocytes in the growth plate and on the deposition of aggrecan and the hypertrophic-specific type X collagen in the cartilaginous matrix.

Animals↗
PubMed1984

Nonenzymatic glucosylation of lysyl and hydroxylysyl residues in type I and type II collagens.

Nonenzymatic glucosylation of type I and type II collagens was examined by incubating collagen substrates with D-glucose in vitro. In one set of experiments, unlabeled collagen was incubated with [14C]-glucose and the incorporation of [14C]-radioactivity into protein was determined by TCA precipitation. The incorporation was dependent on the concentration of glucose and the time of incubation. The glucosylated product was also examined by SDS-polyacrylamide slab gel electrophoresis. The results indicated that both alpha 1(I)- and alpha 2(I)-chains of type I collagen were glucosylated and the glucosylation occurred both with native and denatured collagen as substrate. In further studies [3H]-lysine-labeled collagens were glucosylated, the products reduced by NaBH4, and the [3H]-lysine-derived residues were separated by amino acid analyzer. After a 144 h incubation in vitro, 18.9% of [3H]-lysyl residues and 36.5% of [3H]-hydroxylysyl residues in type I collagen were substituted with glucose. In contrast, 47.9% of [3H]-lysyl residues and 68.1% of [3H]-hydroxylysyl residues in type II collagen were glucosylated after 144 h incubation. Based on quantitative amino acid analyses of the substrates, these values represent 27.6 lysine plus hydroxylysine residues substituted per triple-helical type I collagen molecule and 65.3 residues per triple-helical type II collagen molecule. Thus, type I and type II collagens display differential susceptibilities to nonenzymatic glucosylation. Finally, [3H]-proline-labeled type I collagen was glucosylated to varying extents, and the glucosylated products were used as substrates for human polymorphonuclear leukocyte collagenase. No difference in susceptibility to this collagenase was noted, irrespective of the extent of glucosylation.

Amino Acids↗
PubMed2002

Type II collagen deposition in cruciate ligament precedes osteoarthritis in the guinea pig knee.

OBJECTIVE: To examine the collagens in cruciate ligaments of young Dunkin-Hartley guinea pigs, to determine whether a change in specific collagen types is an early feature of the spontaneous osteoarthritis (OA), which consistently develops in the medial compartment of the knee in this strain. DESIGN: Collagen types I, II, III, IX, and XI were detected by immunofluorescence microscopy in the anterior and posterior cruciate ligaments of animals at 3, 4-5 and 12 weeks of age. Type II collagen in PCL was further analysed by confocal microscopy or biochemical assay after cyanogen bromide digestion, SDS-PAGE and immunoblotting. Interfibrillar proteoglycans were visualized by transmission electron microscopy. RESULTS: Collagen types I and III formed the bulk of fibrous mid-ligament tissue in all animals. Typical cartilage collagens, types II, IX and XI, were identified by immunolabeling where ligaments attached to tibial bone. Type II collagen, normally restricted to the fibrocartilage attachment sites, was also found at separate foci in anterior fiber bundles of the posterior cruciate ligament in 12-week-old animals. Biochemical data confirmed these observations which, together with electron microscopy showing large atypical proteoglycan structures, suggested the deposition of fibrocartilage within the fibrous mid-ligament. CONCLUSIONS: Cruciate ligaments, especially posterior cruciate ligament in Dunkin-Hartley guinea pigs synthesize cartilage-like matrix in mid-ligament prior to the appearance of classical signs of OA.

Aging↗
PubMed2001

Granulocyte-macrophage colony stimulating factor activates proteoglycan, type II collagen, and cAMP production by rat articular chondrocytes through specific binding sites.

OBJECTIVE: To evaluate the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on rat articular chondrocyte (AC) with respect to DNA synthesis, collagen type II and proteoglycan (PG) synthesis and expression, and cAMP production; to examine these cells for the presence of GM-CSF-specific binding sites; and to study their regulation by growth factors and cytokines. METHODS: First passage monolayers of rat AC were incubated with various concentrations of recombinant human GM-CSF, and then [3H]-thymidine, [3H]-proline, and [35S]SO4 incorporation and cAMP production were measured. The density of GM-CSF-specific binding sites, the effects of growth factors and cytokines on receptor density, and the activation of certain post-receptor signaling pathways were also examined by labeling the cell monolayers with [125I]-GM-CSF. RESULTS: GM-CSF (6-100 U/ml) inhibited (30%) [3H]-thymidine incorporation into DNA, and, in contrast, stimulated up to 3.6- and 2-fold [35S]SO4 and [3H]-proline incorporation into glycosaminoglycan side chains and collagen molecules, respectively. GM-CSF also increased aggrecan and type II collagen (Coll II) transcripts by 2- to 3-fold, respectively. These effects were associated with a concentration-dependent increase in cAMP production. A single class of high affinity (Kd = 98 pM; Bmax = 7.08 pM/microg DNA) binding sites of about 220 kDa were found. The [125I]-GM-CSF binding to the cells was slightly increased with phorbol 12-myristate 13-acetate (PMA), insulin-like growth factor-I, platelet derived growth factor, basic fibroblast growth factor, and tumor necrosis factor-alpha, and decreased with pertussis toxin, cholera toxin, and interleukin-1beta. CONCLUSION: These results suggest that GM-CSF may play a role in the regulation of chondrocyte metabolism as an anabolic agent and may stimulate cartilage healing under pathological conditions.

Animals↗
PubMed1995

A radiographic, morphologic, biochemical and molecular analysis of a case of achondrogenesis type II resulting from substitution for a glycine residue (Gly691-->Arg) in the type II collagen trimer.

The type II collagenopathies form a continuous spectrum of clinical severity, ranging from lethal achondrogenesis type II and hypochondrogenesis, through spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia and Kniest dysplasia to the Stickler syndrome and familial precocious osteoarthropathy at the mildest end of the spectrum. We have carried out a radiographic, morphologic, biochemical and molecular study in a case of achondrogenesis type II. Electron micrographs showed inclusion bodies of dilated rough endoplasmic reticulum in the chondrocytes and the presence of sparse collagen fibers in the cartilage matrix. Protein analysis of collagen from cartilage indicated posttranslational overmodification of the major cyanogen bromide peptides, and suggested a mutation near the carboxyl terminus of the type II collagen molecule. Analysis at the DNA level demonstrated that the phenotype was produced by a single base change (G-->C) that resulted in the substitution of glycine691 by arginine in the type II collagen triple helical domain. We confirm previous observations in three cases of hypochondrogenesis that glycine substitutions in the alpha 1(II) chain can result in a phenotype at the most severe end of the type II collagenopathy spectrum.

Abortion, Induced↗
PubMed1996

An alpha 1(II) Gly913 to Cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis.

A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly913 in the alpha 1(II) chain of type II collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type II collagen into the proposita's cartilage, which contained predominantly type I and III collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by the patient's chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and III collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type II collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type II collagen.

Adult↗
PubMed1987

Tissue-specific expression of the human type II collagen gene in mice.

Type II collagen is crucial to the development of form in vertebrates as it is the major protein of cartilage. To study the factors regulating its expression we introduced a cosmid containing the human type II collagen gene, including 4.5 kilobases of 5' and 2.2 kilobases of 3' flanking DNA, into embryonic stem cells in vitro. The transformed cells contribute to all tissues in chimeric mice allowing the expression of the exogenous gene to be studied in vivo. Human type II collagen mRNA is restricted to tissues showing transcription from the endogenous gene and human type II collagen is found in extracellular matrix surrounding chondrocytes in cartilage. The results indicate that the cis-acting requirements for correct temporal and spatial regulation of the gene are contained within the introduced DNA.

Animals↗
PubMed1993

Variable region gene selection of immunoglobulin G-expressing B cells with specificity for a defined epitope on type II collagen.

Immunization with type II collagen (CII) induces collagen-induced arthritis (CIA) in animals, and B cells reactive with CII are involved in the induction and manifestation of the disease. In this study, B cell hybridomas producing IgG antibodies specific for a major epitope on mouse CII (the "C1" epitope, amino acid 316-333), were isolated 11 days after immunization from draining lymph nodes in DBA/1 mice. Injection into neonatal mice of purified and biotinylated monoclonal antibodies binding the C1 epitope led to a specific binding to joint cartilage, demonstrating that the antibodies interact with native antigen in vivo. cDNA sequencing of the B cell clones revealed that they all expressed the same combination of a variable heavy chain (VH J558 family) and light chain (V kappa 21 family) germ-line gene, apparently lacking somatic mutations. The presence of isotype-switched B cells expressing a certain combination of V genes encoding antibodies that bind epitopes in vivo, indicates that this B cell population has been peripherally selected.

Amino Acid Sequence↗
PubMed1997

Selective increased presentation of type II collagen by leupeptin.

Type II collagen (CII) is an arthritogenic self antigen in DBA/1 (H-2q) mice. To analyze the intracellular processing of this fibrillar protein in the context of I-Aq molecules, we have generated hybrid antigen-presenting cells (APC) by fusion of B lymphoma (A20 and M12) cells with CII-primed spleen cells from DBA/1 mice. Efficient presentation of CII by these APC to specific T cell hybridomas required prior cleavage of the antigen and intracellular handling of the peptides. Inhibition of protein transport by brefeldin A prevented the presentation of CII peptides to T cell hybridomas, indicating that the intracellular presentation of CII was dependent on neo-synthesis of I-Aq molecules. In contrast, exposure of hybrid B lymphomas to leupeptin, a protease inhibitor, induced a dose-dependent increase of CII-specific T cell response, while abrogating the I-Aq-restricted presentation of ovalbumin. The enhancing effect of leupeptin was also observed when immune B cells were used as APC. In contrast, leupeptin inhibited the presentation of CII peptides by macrophages or total spleen cells. Pulse-chase analysis of metabolically labeled hybrid APC and immunoprecipitation with antibodies specific for class II molecules or invariant (li) chain revealed that leupeptin did not affect the li chain processing or the formation of stable class II dimers. The stimulatory effect of leupeptin observed on CII presentation suggests that leupeptin protects CII epitopes by interfering with proteases involved in the intracellular degradation of CII.

Animals↗
PubMedDate not supplied

Enhancement (by native type II collagen) of the humoral immune response to native type I collagen in the rat.

Both native type II collagen and rabbit IgG were good immunogens in the rat when emulsified in incomplete Freund's adjuvant but native type I collagen and denatured type II collagen were not. Both native type II collagen and rabbit IgG had an enhancing effect upon the production of antibodies to native type I collagen when rats were immunised with a mixture of native type I collagen and either of these immunogens but denatured type II collagen did not have this effect. These immunogens, however, did not enhance the production of antibodies to ovalbumin when emulsified with it. Although both native type II collagen and rabbit IgG showed this enhancing effect with native type I collagen, only rats immunised with native type II collagen or mixtures containing native type II collagen developed arthritis. Thus, a specific immune response to collagen rather than this enhancing effect appears to be necessary for the induction of arthritis.

Animals↗
PubMed1990

Virulent Escherichia coli strains for chicks bind fibronectin and type II collagen.

125I-fibronectin and 125I-collagen (type II) binding was detected in Escherichia coli strains isolated from chickens and poults. High fibronectin binding-strains also bind the 29 kD aminoterminal fragment of fibronectin. Binding properties in strain CK28 were partially characterized. The highest binding of 125I-fibronectin and 125I-collagen for strain CK28 was obtained with bacteria grown at 33 degrees C. Binding of 125I-fibronectin, its 125I-29 kD fragment, and 125I-collagen, was very rapid, reaching a maximum in 5 min. Binding of 125I-fibronectin and 125I-collagen was considerably inhibited by preincubation of bacteria with unlabelled fibronectin and unlabelled type I collagen respectively, but not inhibited with human immunoglobulin G or bovine serum albumin. Inhibition experiments showed that the reversibility of 125I-fibronectin binding was estimated at approximately 50%, while reversibility for 125I-collagen binding was higher than 90%. Receptors for fibronectin, its 29 kD fragment, and collagen were released from the bacterial surface by treatment at different temperatures, and surface material released at 100 degrees C inhibited binding. There was cross-inhibition for both fibronectin and collagen binding when unlabelled fibronectin and unlabelled collagen were used as inhibitors, suggesting that binding receptors for both proteins may be closely located.

Animals↗
PubMed1995

Cartilage type II collagen fibrils show distinctive negative-staining band patterns differences between type II and type I unfixed or glutaraldehyde-fixed collagen fibrils.

The cross striation of native and reconstituted collagen fibrils is believed to conform to a unique D-band pattern independently of the genetically distinct types of fibril-forming collagens. This investigation focuses on type II native collagen fibrils, whose negative-staining patterns are shown to differ from the usual banding exhibited by type I collagen fibrils. Negative staining with phosphotungstic acid, pH 7.4, was carried out on a) unfixed and b) glutaraldehyde-fixed collagen fibrils isolated from bovine hyaline cartilages. The band patterns obtained and their microdensitograms were compared to similarly processed type I collagen fibrils isolated from bovine fibrous tissues. Only minor differences were observed in unfixed fibrils. In the intraperiod light zones of type II fibrils, two dark bands (interbands X2-Y4 and Y4-Y2) showed different intensities with respect to their homologous bands in type I fibrils. In contrast, a marked difference was shown by glutaraldehyde-fixed fibrils. In comparison with type I fibrils, the greater stain exclusion capacity of type II fibrils yielded both the appearance of supernumerary bands, which altered banding in two intraperiod regions, and differences in the intensity of several bands in three intraperiod regions where the band distribution was similar. This stain exclusion pattern may be accounted for by molecular extradensity. The possibility that it depends on linkage with a higher number of glutaraldehyde residues and/or the persistence of cross-linked collagenic or non-collagenic proteins is discussed. To refer to the glutaraldehyde-induced band patterns in negatively stained type II and type I collagen fibrils, the terms "bands GA(II) 1-12" and "bands GA(I) 1-15," respectively, are proposed.

Animals↗
PubMed2004

A type XI collagen mutation leads to increased degradation of type II collagen in articular cartilage.

OBJECTIVE: To determine in articular cartilage whether degraded type II collagen is more abundant in Col11a1 mutant cho/+ than in age-matched +/+ mice and whether collagen degradation occurs in a generalized or localized fashion. DESIGN: Knee joints from cho/+ and +/+ mice at 6, 9, 12 and 15 months of age were dissected, fixed, cryosectioned, and stained with antibody COL2-3/4m against denatured type II collagen using a FITC-conjugated secondary antibody. Sections were viewed and photographed under a fluorescence microscope and areas of staining were quantified. RESULTS: Before 12 months of age, little degraded collagen staining was detectable in +/+ or cho/+ mice. By 15 months, however, cho/+ mice showed significantly more degraded type II collagen than age-matched controls. Degraded collagen staining was localized at the articular surface, not distributed generally throughout the articular cartilage. CONCLUSIONS: The results suggest a model in which cumulative biomechanical stresses trigger increased collagen synthesis and degradation in both +/+ and cho/+ mice at around 12 months of age. Cho/+ mice, however, are less able to synthesize and assemble normal replacement collagen fibrils because of the Col11a1 mutation. Degradation is further activated, resulting in the accumulation of degraded type II collagen in the articular cartilage extracellular matrix. Similar mutations that do not overtly affect skeletal development may likewise predispose humans to increased collagen degradation and resultant osteoarthritis.

Animals↗
PubMed1985

Collagen-induced arthritis in mice. Localization of an arthritogenic determinant to a fragment of the type II collagen molecule.

Purified chick type II collagen was cleaved with cyanogen bromide (CB), and the resulting peptides isolated and renatured. Sera from arthritic DBA/1 mice, immunized with chick type II collagen, were tested for reactivity with each peptide. The sera preferentially recognized peptides 11, 10, and 8, in that order. Some reactivity was also detected to peptides 9, 7, and 12. Because arthritis depends upon binding of antibody to autologous type II collagen in the joint, sera were also tested for reactivity with mouse type II collagen. There was a strong positive correlation between reactivity with peptide 11 and reactivity with mouse collagen, but no correlation was found with any of the other peptides. Peptides 11, 10, and 8 were also used for immunization. Antibodies were detected in response to each of these peptides, but arthritis developed only in mice immunized with peptide 11. We conclude that a major immunogenic and arthritogenic epitope on type II collagen resides in the region of the molecule represented by CB peptide 11.

Animals↗