title: A human leucocyte antigen-DR1 transgene confers susceptibility to experimental allergic encephalomyelitis elicited by an epitope of myelin basic protein.
abstract: Much evidence now indicates that human leucocyte antigen (HLA) class I and class II transgenic (Tg) mice can be of value in analysing HLA-restricted presentation of T-cell epitopes relevant to experimental models of autoimmune diseases. One area where this has been applied is the characterization of myelin epitopes presented by HLA class II molecules in experimental model of multiple sclerosis (experimental allergic encephalomyelitis (EAE)). As a first step towards humanized disease models in HLA Tg mice, we have analysed immune response of lymph node cells of HLA-DR1 Tg mice immunized with the human myelin basic protein (MBP) peptides 13-33, 87-106 and 139-154 bound by HLA-DR1. We report here that HLA-DR1 Tg mice display a hierarchy of response in vivo and in vitro to MBP epitopes depending on the binding affinity to DRB*0101 molecule. In fact, the 13-33 epitope induced a strong T helper 1 (Th1) response accompanied by high T-cell precursor frequency and caused mild EAE, while the two other epitopes gave poor (139-154) or no disease (87-106), and these data correlate with in vitro Th1 response. These data could prove a useful tool in understanding the role played by different MBP epitopes in EAE.
authors.affiliation: Department of Biopathology, University of Palermo, Corso Tukory 211, 90134 Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Sireci
authors.forename: F
authors.initials: F
authors.lastname: Dieli
authors.forename: N
authors.initials: N
authors.lastname: Caccamo
authors.forename: A
authors.initials: A
authors.lastname: Barera
authors.forename: P
authors.initials: P
authors.lastname: Carta
authors.forename: C
authors.initials: C
authors.lastname: Di Sano
authors.forename: S
authors.initials: S
authors.lastname: Meraviglia
authors.forename: C T
authors.initials: CT
authors.lastname: Bonanno
authors.forename: A
authors.initials: A
authors.lastname: Salerno
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D020022:Genetic Predisposition to Disease; D015798:HLA-DR1 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology*; D004676:Myelin Basic Protein / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology
chemical_list: D018984:Epitopes, T-Lymphocyte; D015798:HLA-DR1 Antigen; D004676:Myelin Basic Protein; D010446:Peptide Fragments