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Biomedical subjects

H Offner

Publications and source records attributed to H Offner.

At least 91 records · Page 5Linked to original sources
PubMed1993

Induction of experimental autoimmune encephalomyelitis in severe combined immunodeficient mice reconstituted with allogeneic or xenogeneic hematopoietic cells.

Severe combined immunodeficient (SCID) C.B-17-scid/scid (H-2d) strain mice are deficient for T and B lymphocytes and lack all of the immune functions associated with these cell types. Experimental autoimmune encephalomyelitis (EAE) was induced in chimeric SCID mice that had been previously reconstituted with allogeneic mouse or xenogeneic rat hematopoietic stem cells from EAE-susceptible donor strains. Encephalitogenic, myelin Ag-specific, T lymphocytes selected from SJL mice, Lewis rats, or Buffalo rats transferred passive EAE into chimeric SCID mice reconstituted with SJL mouse, Lewis rat, or Buffalo rat hematopoietic cells, respectively. SCID mice reconstituted with Lewis rat hematopoietic tissue and thymus were also susceptible to EAE induced by active immunization with the myelin proteolipid protein synthetic peptide PLP S139-151. T lymphocytes recovered from the spleens of SCID mouse-rat chimeras with EAE proliferated upon in vitro stimulation with myelin Ag presented by APC syngeneic to the transplant donor, and rat T lymphocytes selected in vitro from SCID mouse-rat chimeras with EAE transferred EAE back into naive recipient rats. Thus, the immunodeficiency present in SCID mice can be overcome at least partially by hematopoietic tissue transplantation from allogeneic or xenogeneic donors. Furthermore, allogeneic SJL mouse and xenogeneic Lewis or Buffalo rat myelin Ag-specific T cells can transfer EAE between strains and species, respectively, into recipient SCID mouse chimeras.

Amino Acid Sequence↗
PubMed1993

Lymphokine mRNA expression in the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis is associated with a host recruited CD45R hi/CD4+ population during recovery.

To evaluate CD4+ T cell subpopulations involved in the induction and recovery from experimental autoimmune encephalomyelitis (EAE), the CD45R phenotype and lymphokine mRNA profile was evaluated for encephalitogenic CD4+ T cell lines in vitro and compared to CD4+ T cells isolated from the spinal cord of Lewis rats with EAE. All of the myelin basic protein (MBP)-specific T cell lines and clones that adoptively transferred EAE were > 90% CD4+ and > 90% CD45R lo. A time course of EAE disease progression was monitored as a function of the percentage of CD45R hi/CD4+ T cells isolated from the spinal cords of diseased animals. The majority of CD4+ T cells found in the central nervous system during the early phase of passive EAE were CD45R lo (the same as the encephalitogenic lines/clones). A large increase of the CD45R hi/CD4+ T cells (up to 45%) was observed during the peak and recovery phases of EAE. Lymphokine mRNA production was analyzed from antigen-stimulated MBP-specific lines, and from spinal cord lymphocytes isolated from rats with EAE. The BP-specific lines produced Th1 lymphokines (IL-2, IFN-gamma, and TNF-alpha), while the spinal cord lymphocytes produced the same Th1 lymphokines as well as IL-4 and IL-10. The CD45R hi/CD4+ T cells isolated from the spinal cords were larger and expressed more lymphokine RNA per cell than the CD45R lo/CD4+ T cells. The encephalitogenic cells (CD45R lo) were detected in the spinal cords of rats with a fluorescent dye and by allelic transfers and all of the CD45R hi/CD4+ T cells were found to be host recruited. Thus, it appears that the CD45R hi/CD4+ lymphocytes found in the spinal cord represent a host-recruited, activated cellular infiltrate that increased in number in the recovery phase of EAE and synthesized both Th1 and Th2 lymphokines.

Animals↗
PubMed1993

Epitope specificity and V gene expression of cerebrospinal fluid T cells specific for intact versus cryptic epitopes of myelin basic protein.

Recent evidence supports the possible involvement of myelin basic protein (BP) as one of the target autoantigens in multiple sclerosis (MS), including elevated frequencies of MS blood and cerebrospinal fluid (CSF) T cells, and the presence in MS plaque tissue of V beta gene sequences and CDR3 motifs characteristic of BP-reactive T cells. Because of its proximity to the target organ, the CSF has long been thought to harbor T cells involved in the pathogenic process. In order to evaluate their frequency and response characteristics, BP-reactive T cells were isolated by limiting dilution from the CSF of patients with MS and other neurological diseases (OND) for quantitation and determination of epitope specificity and V alpha and V beta gene expression. In addition to isolates responsive to intact BP epitopes that were present at a significantly higher frequency in MS versus OND CSF, we here describe a second clonotype responsive to 'cryptic' BP epitopes that is present at approximately equal frequencies in MS and OND patients. In spite of their difference in recognition of intact versus 'cryptic' BP determinants, both clonotypes predominantly recognized epitopes in the N terminal half of human BP, using a similar V gene repertoire that included biased use of V alpha 2 and to a lesser degree V beta 7 and V beta 18. These V gene biases were not related to the epitope specificity of the T cells, indicating that V gene selection is not epitope-driven. These data suggest that there is differential recognition of intact versus 'cryptic' BP determinants in MS versus OND patients that may be related to the processing and presentation of BP to the immune system.

Adult↗
PubMed1993

Ganglioside (GM1) distinguishes the effects of CD4 on signal transduction through the TCR/CD3 complex in human lymphocytes.

Ganglioside (GM1) modulation of CD4 off the surface of T lymphocytes defined functions of the CD4 molecule during signal transduction through the T cell receptor (TCR)/CD3 complex. Antibody cross-linking of CD3 alone (3 x 3) stimulated phospholipase C (PLC) activity, rapid Ca2+ flux, and protein phosphorylations in freshly isolated human T lymphocytes. Antibody cross-linking of CD4 and CD3 (3 x 4) stimulated greater signaling than that caused by 3 x 3. Cross-linking CD4 alone did not stimulate these signaling processes. GM1-modulation of CD4 from the cell surface blocked all aspects of the augmented signaling imparted by CD4 co-modulation with CD3. In comparison, pretreatment with the protein tyrosine kinase inhibitor genistein inhibited 3 x 4-stimulated PLC activity and protein phosphorylation but not Ca2+ flux. Antibody cross-linking of the tyrosine phosphatase CD45 with 3 x 4 (3 x 4 x 45) also inhibited CD4-augmented phosphorylations and like genistein did not reduce Ca2+ levels. In conclusion, these data demonstrate that CD4 can augment signal transduction through the TCR/CD3 complex by its physical proximity to CD3. TCR/CD3-signaling augmentation by CD4 stimulated protein tyrosine kinases and PLC activities but stimulated intracellular Ca2+ flux through an independent mechanism(s).

CD4 Antigens↗
PubMed1992

Spontaneous development of protective anti-T cell receptor autoimmunity targeted against a natural EAE-regulatory idiotope located within the 39-59 region of the TCR-V beta 8.2 chain.

The development of experimental autoimmune encephalomyelitis (EAE) in Lewis rats is mediated by V beta 8.2+ T cells specific for myelin basic protein. One consequence of this biased expression of V beta 8.2 is the spontaneous development of regulatory T cells and antibodies against residues 39-59 of the V beta 8.2 sequence. Moreover, a synthetic V beta 8.2-39-59 peptide could induce protection against and speed recovery from EAE. T cells and antibodies specific for V beta 8.2-39-59 could transfer protection from EAE. Recently, we reported that the protective T cell epitope is subsumed within the V beta 8-44-54 sequence. We now report that protection induced by V beta 8-44-54 lasted at least 102 days and produced "split tolerance," enhancing anti-myelin basic protein antibody titers but reducing anti-myelin basic protein T cell frequency. The shorter V beta 8-44-54 peptide induced a distinct set of antibodies that did not cross-react with the longer V beta 8.2-39-59 peptide, although both specificities could stain V beta 8.2+ T cells and were equally protective against EAE. However, the V beta 8.2-39-59 peptide, but not the V beta 8-44-54 peptide, would appear to represent the natural idiotope: antibodies to V beta 8.2-39-59 that develop spontaneously during EAE could be boosted to higher titers only by the V beta 8.2-39-59, but not by other TCR peptides from the V beta 8.2 sequence, including V beta 8-44-54 that contains the functional T cell epitope. These results suggest that natural processing of the TCR V beta-chain favors the formation of a peptide that resembles the V beta 8.2-39-59 sequence. The B cell epitope present on the V beta 8-44-54 sequence was evident only in the absence of residues 39-43 and 55-59, suggesting that the two peptides possess distinct conformations. However, the V beta 8-44-54 B cell epitope is most likely expressed on the V beta 8.2+ T cells, either as a low affinity determinant on the intact TCR alpha/beta heterodimer or as a cryptic epitope bound in the cleft of surface MHC molecules.

Amino Acid Sequence↗
PubMed1992

Transforming growth factor-beta enhances the in vivo effector function and memory phenotype of antigen-specific T helper cells in experimental autoimmune encephalomyelitis.

Transforming growth factor-beta (TGF-beta) had a profound effect on the in vitro phenotypic development of Ag-activated Th cells and enhanced the in vivo effector function of these cells upon adoptive transfer. Previous studies have shown that there are two types of Th cell populations found in unimmunized animals, naive helper cells, which are short-lived and express low levels of CD44 and high levels of CD45R and Mel-14, and memory helper cells, which have a long life span and express high levels of CD44 and low levels of CD45R and Mel-14. Culturing of Ag-specific murine Th cell lines and clones in the presence of TGF-beta greatly enhanced both the memory phenotype of the cultured cells and the effector function upon adoptive transfer in experimental autoimmune encephalomyelitis. Histologic evaluation of spinal cords from recipients receiving passively transferred murine T cell lines cultured with TGF-beta revealed large demyelinated plaques (multiple sclerosis-like) that were not present in animals receiving cells cultured with Ag alone. TGF-beta also enhanced the capability of myelin basic protein-specific Lewis rat T cell lines to transfer experimental autoimmune encephalomyelitis and potentiated a purified protein derivative-specific rat helper cell line to transfer delayed type hypersensitivity. Thus, the effects of TGF-beta did not appear to be limited by species specificity, Ag specificity, or in vivo T cell function. This is the first study showing that TGF-beta can potentiate the development and maintenance of the Th cell memory phenotype in vitro and enhance their in vivo effector function in an animal disease model.

Animals↗
PubMed1992

Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. I. T cell receptor peptide regulation of T cell clones expressing cross-reactive V beta genes.

In Lewis rats, immunization with myelin basic protein induces two distinct encephalitogenic T cell populations, those responding to the immunodominant 72-89 epitope and those specific for a secondary epitope including residues 87-99. The 72-89 specific T cells were I-A restricted and preferentially expressed V beta 8.2 in their TCR. To determine the fine specificity, MHC restriction, and TCR V beta gene use in T cells reactive to the secondary epitope, we characterized 23 T cell clones from the lymph nodes (LN) and spinal cords (SC) of rats immunized with either whole basic protein or synthetic peptides S85-99 and S87-99 that were found to be functionally similar. The S85-99/S87-99 specific clones from LN and SC were all encephalitogenic despite differences in recognition of intact basic protein and class II MHC restriction. Unlike LN clones that overexpressed V beta 8 (46%+) and V beta 6 (31%+), however, SC clones were strongly biased (86%+) in their expression of V beta 6. This V gene bias raised the possibility of TCR peptide therapy using V beta 6 peptides. The V beta 6 sequence was similar to V beta 8.2 in the CDR2 region, and the corresponding peptides from this region were found to be cross-reactive in vivo. Moreover, both peptides were effective in the treatment of EAE induced with either S85-99, biased in V beta 6+ and V beta 8+ T cells, or guinea pig basic protein, biased only in V beta 8+ T cells. These data demonstrate the presence of common immunogenic epitopes among subsets of TCR V region gene families that possess important regulatory activity on effector T cell function.

Amino Acid Sequence↗
PubMed1992

Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells.

The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B class II molecule of the MHC and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V beta gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple V beta genes including V beta 6. This difference in heterogeneity of V beta usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord clones revealed a conserved amino acid motif also found in the majority of V beta 6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with V beta 8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR V beta usage in peripheral T cells responding to an autoantigen does not always predict the V beta usage among T cells at the site of an autoimmune attack. Possible explantations for the relative homogeneity in TCR V beta expression seen in T cell clones derived from the spinal cord are discussed.

Amino Acid Sequence↗
PubMed1992

Common sequence on distinct V beta genes defines a protective idiotope in experimental encephalomyelitis.

Synthetic TCR peptides expressed by encephalitogenic T cells can induce both cellular and humoral responses that protect against experimental encephalomyelitis. In the Lewis rat, encephalitogenic T cells predominantly express V beta 8.2, and a peptide in the CDR2 region representing residues 39-59 could both protect against and treat experimental autoimmune encephalitis (EAE). Similarly, the homologous and cross reactive 39-59 peptide from V beta 8.6 expressed by an EAE-protective clone also had protective and therapeutic activity against EAE. The consensus sequence between the V beta 8.2 and V beta 8.6 peptides, which included residues 44-54, was postulated to contain the protective idiotope. In this report, we demonstrate that this peptide, designated V beta 8-44-54, has comparable activity to the longer peptides for treating both active and passive EAE. Similar to the longer V beta 8.2-39-59 peptide, the V beta 8-44-54 peptide stimulates protective TCR peptide-specific CD4+, CD8dim T cells restricted by MHC I. We also report for the first time the recovery of V beta 8-44-54 reactive T cells that express a variety of V beta genes in their T-cell receptor (TCR), including V beta 4, 8, 10, 12, 15, 17, 19, and 20. Taken together, these data establish that the V beta 8-44-54 sequence constitutes an important autoregulatory idiotope in EAE.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1992

The synthetic 87-99 peptide of myelin basic protein is encephalitogenic in Buffalo rats.

A synthetic peptide corresponding to residues 87-99 (S87-99) of myelin basic protein (BP) induced the proliferation of an encephalitogenic, BP-specific T cell line selected in vitro from inbred Buffalo-strain rats (RT1b). Active immunization with guinea pig (GP)-BP or S87-99 in complete Freund's adjuvant (CFA) and intravenous pertussigen induced acute experimental autoimmune encephalomyelitis (EAE) 10-12 days after immunization. Fifty percent of recovered rats developed a single relapse 17-21 days after immunization. T lymphocytes selected in vitro with S87-99 transferred acute, non-relapsing EAE into naive recipients. Histological examination during acute EAE revealed foci of inflammatory cells associated with demyelination in the spinal cords and peripheral nerve roots. Thus, as in several other rodent strains, the 87-99 region of BP is antigenic and encephalitogenic in the inbred Buffalo-strain rat. Additionally, the 87-99 sequence of GP-BP was predicted to be antigenic by two different methods. These results suggest that the 87-99 region of BP, which is highly conserved among mammalian species, may be widely encephalitogenic due to antigen-intrinsic properties.

Animals↗
PubMed1992

Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis.

T cell sensitization to two myelin components, myelin basic protein (MBP) and myelin proteolipid protein (PLP), may be important to the pathogenesis of multiple sclerosis (MS). Using the limiting dilution assay, we demonstrated that the blood of MS patients had an increased frequency of MBP-reactive T cells compared with normal subjects and patients with other neurological diseases (OND) and rheumatoid arthritis. There was no difference in T cell frequency to a synthetic peptide, PLP139-151, or Herpes simplex virus. Within cerebrospinal fluid (CSF), 37% of IL-2/IL-4-reactive T cell isolates from MS patients responded either to MBP or PLP139-151 while only 5% of similar isolates from OND patients responded to these myelin antigens. The mean relative frequency of MBP-reactive T cells within CSF from MS patients was significantly higher than that of OND patients (22 x 10(-5) cells versus 1 x 10(-5) cells) and was similar to that of MBP reactive T cells within the central nervous system of rats with experimental autoimmune encephalomyelitis. These results lend new support to the hypothesis that myelin-reactive T cells mediate disease in MS.

Amino Acid Sequence↗
PubMed1992

TCR peptide therapy decreases the frequency of encephalitogenic T cells in the periphery and the central nervous system.

The V beta 8 CDR2 consensus peptide, residues 44-54, is highly effective in the treatment of clinical experimental autoimmune encephalomyelitis (EAE) in Lewis rats. To monitor immunological changes during EAE resulting from TCR peptide therapy, the frequencies of encephalitogenic and regulatory T cells were quantitated in lymph nodes, blood, and spinal cord. The frequency of T cells specific for basic protein and its major encephalitogenic epitope, residues 72-89, increased during EAE to about 1 cell per 100,000 lymph node or blood cells at the peak of clinical disease, and then declined. In contrast, the frequency of these T cells in spinal cord was highest, 50 per 100,000, prior to onset of clinical signs, and then decreased rapidly prior to spontaneous recovery. Injection of 100 micrograms of TCR V beta 8-44-54 peptide caused a decrease within 1-5 days in the frequencies of guinea pig basic-protein (GP-BP) and 72-89-reactive T cells in blood and spinal cord, and in the total number of infiltrating cells in spinal cord. In lymph nodes, 72-89-reactive T cells decreased as T cells specific for a protective epitope, residues 55-69 of GP-BP increased, suggesting epitope switching at the site of GP-BP immunization. Conversely, the frequency of T cells specific for the V beta 8-44-54 peptide increased, especially in blood and spinal cord, whereas T cell frequencies to control antigens were unchanged. These data document the critical presence of encephalitogenic T cells within the spinal cord during clinical EAE, and demonstrate that rapid and profound changes in T cell frequencies in the periphery and spinal cord are triggered by TCR peptide therapy.

Amino Acid Sequence↗
PubMed1992

T cell receptor peptide therapy for autoimmune disease.

Synthetic peptides corresponding to germline T cell receptor (TCR) V beta sequences shared by encephalitogenic T cells can prevent and treat experimental autoimmune encephalomyelitis in rats. The operative mechanism apparently involves boosting of anti-TCR immunity that develops during the course of experimental autoimmune encephalomyelitis (EAE), leading to the induction of autoregulatory T cells and antibodies. Striking parallels are present between patients with multiple sclerosis and animals with EAE in the T cell frequency and TCR V gene bias of BP reactive T cells, suggesting the involvement of an encephalitogenic process in multiple sclerosis. Preliminary trials with the appropriate human TCR peptides indicate that anti-TCR immunity can be boosted efficiently and safely, with concomitant loss of BP response, thus providing an effective strategy for selective regulation of autoimmunity in man.

Animals↗
PubMed1992

Human CD8+ T cell clone regulates autologous CD4+ myelin basic protein specific T cells.

Normal human CD8+ T cell clones were co-isolated from the same culture wells as CD4+ T effector cell clones specific for myelin basic protein (MBP). Microcultures from which the CD8+ clones were isolated initially proliferated weakly to whole MBP and to an MBP peptide spanning residues 90-170. This pattern of response was similar to strongly proliferating wells that yielded CD4+ T cell clones specific for the 90-170 peptide. After repeated stimulation, however, no response to MBP or MBP 90-170 was detected, even though the number of cells increased after stimulation. Phenotyping and TCR analyses revealed the presence of two CD8+, CD4-, IL-2R+ T cell isolates that expressed a single V beta gene (V beta 17) that differed from the CD4+ isolates that uniformly expressed V beta 14. One of these CD8+ clones (C9) inhibited the antigen-driven proliferation of an autologous MBP 90-170 reactive clone but not an autologous clone specific for Herpes simplex virus (HSV), without affecting MHC non-restricted mitogen responses of the same clones. Moreover, C9 did not inhibit heterologous CD4+ T cell clones specific for MBP 1-38 or 90-170. A culture supernatant of the CD8+ clone showed the same pattern but lower levels of inhibition. C9 had mild cytolytic activity when incubated at high ratios with an autologous MBP-specific CD4+ clone. Lysis was blocked completely by anti-MHC class I antibodies, but not by anti-MHC II antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Analysis of T cell receptor beta chains in Lewis rats with experimental allergic encephalomyelitis: conserved complementarity determining region 3.

This study explores the usage of T cell antigen receptor (TCR) beta chain elements in Lewis rats with experimentally induced allergic encephalomyelitis (EAE). TCRs from 15 different T cell clones and hybridomas derived from animals immunized with myelin basic protein (MBP), and all having specificity for the 21-mer encephalitogenic fragment MBP 68-88, utilized V beta 8.2. In addition, there was a marked conservation of the first two amino acid residues of the junctional complementarity determining region 3 (CDR3) associated with the V beta 8.2 receptors. 12 of 15 contained an aspartic acid followed by serine regardless of the associated J beta element. At the nucleotide level, this conservation of AspSer residues was accomplished with few or no nongermline-encoded nucleotide (N) additions. A similar pattern of AspSer usage and N region nucleotide additions was observed in a number of V beta 8.2 isolates derived from MBP-immunized lymph nodes. In contrast, V beta 8.2 polymerase chain reaction amplified isolates from Lewis T cells activated with concanavalin A or from lymph nodes of complete Freund's adjuvant-immunized animals showed no AspSer utilization (0/31) in the CDR3, and four to nine N region nucleotide additions. We conclude from this finding that AspSer residues in the CDR3, limited N region nucleotide additions, along with V beta 8.2 sequences, contribute to TCR specificity for MBP 68-88. This raises the possibility that encephalitogenic, disease-causing T cells either represent a population that derives from late fetal life or alternatively, that they are rare cells with this particular TCR phenotype contributed to the T cell pool throughout adulthood and are selected by antigen. In either case, the CDR3 AspSer sequences as well as V beta 8.2 sequences are candidates for the receptor target structures recognized by regulator T cells in recovery from and resistance to active EAE. In this respect, a preliminary analysis of TCR utilization in three T cell clones specific for MBP 68-88 isolated from animals recovered from active EAE indicates that while all three use V beta 8.2, only one contains AspSer in the CDR3.

Amino Acid Sequence↗
PubMed1991

Location of a new encephalitogenic epitope (residues 43 to 64) in proteolipid protein that induces relapsing experimental autoimmune encephalomyelitis in PL/J and (SJL x PL)F1 mice.

Synthetic peptides of proteolipid protein (PLP) were screened for their ability to induce experimental autoimmune encephalomyelitis (EAE) in SJL/J, PL/J, and (SJL x PL)F1 mice, and T cell lines were selected by stimulation of lymph node cells with PLP peptides. PLP 141-151 was found to be less encephalitogenic in SJL/J mice than PLP 139-151, due to deletion of two amino acids from the amino-terminal end. PLP 139-151 immunization induced relapsing EAE in SJL/J and F1 mice but not PL/J mice. In contrast, PLP 43-64 induced relapsing EAE in PL/J and F1 mice but not SJL/J mice. F1 T cell lines specific for either PLP 43-64 or PLP 139-151 adoptively transferred demyelinating EAE to naive F1 recipients. Haplotypes H-2s and H-2u appear to be immunologically co-dominant in F1 mice in the PLP EAE system, which differs from the H-2u dominance in F1 mice in the myelin basic protein EAE system. The identification of a PLP peptide that is encephalitogenic in PL/J mice, in addition to the previous demonstration of PLP peptides that are encephalitogenic for SWR mice (PLP 103-116) and SJL/J mice (PLP 139-151), lends support to a role for PLP as a target Ag in autoimmune demyelinating diseases.

Amino Acid Sequence↗