Delineation of the minimal encephalitogenic epitope of proteolipid protein peptide(91-110) and critical residues required for induction of EAE in HLA-DR3 transgenic mice.
Previously, we have reported that proteolipid protein (PLP) peptide 91-110 can induce experimental autoimmune encephalomyelitis (EAE) in HLA-DR3 transgenic (tg) mice. Here we, report that residues spanning 97-108 are the minimal epitope required for induction of EAE in DR3 mice. Utilizing a series of alanine-substituted peptides, positions 99, 101, 102, 103, 104, and 106 are identified as residues necessary for an immune response. Further analysis indicated that amino acid isoleucine (99), aspartate (102) and lysine (104) are anchor residues facilitating binding to HLA-DR3 molecules. These results may have applications in the future design of peptide based immunotherapy.
Mangalam
Ashutosh K
AK
Department of Immunology, Mayo Clinic College of Medicine, 200, 1st Street SW Rochester, MN 55905, USA.
Khare
Meenakshi
M
Krco
Christopher J
CJ
Rodriguez
Moses
M
David
Chella S
CS
D000409:Alanine / Q000276:immunology; D000818:Animals; D001059:Apoproteins / Q000737:chemistry / Q000633:toxicity*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced* / Q000276:immunology*; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007116:Immunization, Passive; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology* / Q000633:toxicity; D008285:Major Histocompatibility Complex / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018448:Models, Immunological; D018991:Myelin Proteolipid Protein / Q000737:chemistry / Q000633:toxicity*; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D001059:Apoproteins; D016207:Cytokines; D015803:HLA-DR3 Antigen; D016056:Immunodominant Epitopes; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D000409:Alanine