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1、Poster Abstracts / Journal of Neuroimmunology 90 (1998) 13-105 33 167 Clonal T-cell Cross-reactivity Between Myelin Antigens MBP and PLP and Human Respiratory Coronavirusesin Multiple Sclerosis A. Boucher, G. Mercier, nstitutArmand-Frappieg Canada, P. Duquette, MS Clinic, Notre Dame Hospital Montrea
2、l Canada, P.J. Talbot, lnstitutArmand-Frappier, Canada Viruses could be involved in the induction of irnmunopathological events associated with multiple sclerosis (MS). For instance, molecular mimicry between viruses and myelin antigens could mediate cross-reactive immune responses leading to autoim
3、mune disease. We previously showed that a human respiratory coronavirus (229E), and myelin basic protein (MBP) activated a large proportion of T-cell lines established from MS patients by in vitro selection with either 229E or MBP. We now report the generation and maintenance of T-cell clones specif
4、ic for MBP, proteolipid protein (PLP) and the two known strains of human coronavirus (229E and OC43). Some of these clones were activated by both coronavirus and myelin antigens, which is consistent with molecular mimicry at the single T-cell level. The observation and further characterization of su
5、ch T-cell clones will bring us closer to an understanding of their potential relevance in MS pathogenesis. (Supported by the Multiple Sclerosis Society of Canada) 170 Expansion by Self Antigen is Necessary for the Induction of Experimental Autoimmune Encephalomyelitis by T Cells Primed with a Cross-
6、reactive Environmental Antigen A.M. Carrizosa. L.B. Nicholson, M. Farzan, HamardMedicalSchool, USA, S. Southwood, A. Sette, E pimmune, USA, R.A. Sobel, Stanford University School of Medicine, USA, V.K. Kuchroo, Harvard Medical School USA Cross-reactivity with environmental antigens has been postulat
7、ed as a mechanism responsible for the induction of autoimmune disease. Experimental autoimmune encephalomyelitis (EAE) is a T cell mediated autoimmune disease model inducible in susceptible strains of laboratory animals by immunization with protein constituents of myelin. We used myelin proteolipid
8、protein (PLP) peptide 139- t51 and its analogs to define motifs to search a protein database for structural homologues of PLP 139-151 and identified five peptides derived from microbial antigens that elicit immune responses that cross-react with this self- peptide. Exposure of naive SJL mice to the
9、cross-reactive environmental peptides alone was insufficient to induce autoimmune disease even when animals were treated with antigen non-specific stimuli (superantigen, LPS). However, immunization of SJL mice with suboptimal doses of PLP 139-151 peptide after priming with cross-reactive environment
10、al peptides consistently induced EAE. These data suggest that expansion by self-antigen is required to break the threshold to autoimmune disease in animals primed with cross- reactive peptides. 168 Immunodominance of Eneephalitogenie Peptide Specific Responses in Lewis, DA, and (Lew x DA)F1 Rats C.R
11、. Wagner, VAMC, USA, D.J. Hinrichs, H.G.A. 139uwcr, gAMe andEACRI, USA Guinea pig MBP-CFA injection leads to the development of EAE in Lewis. DA and (Lew x DA)FI rats. Repeated culture stimulation of Lewis- derived GPMBP-immune cells with GPMBP results in the development of a population of encephali
12、togenic cells that are selected for the 72-84 determinant. Repeated culture stimulation of DA-derived GPMBP-immune cells with GPMIP results in the development of apopulation of encephalitogenic cells that are selected for the 42-55 determinant. Studies with (Lew x DA)Fl-derived GPMBP-immune cells sh
13、ow that repeated stimulation in culture with GPMBP results in the development of art encephalitogenic population that contains 42-55, 72-84 and 85-97-specific subsets. Proliferation assay data suggests that the 85-97-specific response of the (Lew x DA)Fl-derived T-cell line is immunodominant. This m
14、ulti- peCific T-cell line successfully vaccinates (Lew x DA)FI recipients against MBP-CFA induced EAE. We have initiated studies to select GPMBP- immune (Lew x DA)F1 cells specifically responsive to 42-55, 72-84 or 85-97 and to date we have determined that although an encephalitogenic 85-97 specific
15、 (Lew x DA)Fl-derived T-cell line vaccinates (Lew x DA)FI recipients against 85-97-CFA induced disease, this cell line does not vaccinate (Lew x DA)FI recipients against GPMBP-CFA induced EAE. We are continuing these studies in order to determine the efficacy of vaccination induced resistance where
16、the potential to respond to an encephalitogen is influenced by more than a single parental haplotype. 171 Binding Stretches of Myelin Basic Protein Define Encephalitogenie T Cell Epitopes for RTI.B and RT1.DAIleles of Four Different Rat Haplotypes I.L. de Graaf R. Weissert, Karolinska Institute, Sweden, P. Kjellen, IL Holm dalai, Lund University, bSeeden, T. Olsson, Karolinska University, Sweden We have measured the apparent affinity of overlapping 13 mer myelin bas
