Cutting edge: single-chain trimers of MHC class I molecules form stable structures that potently stimulate antigen-specific T cells and B cells.
We report in this work the expression and characterization of class I molecules expressed as single-chain trimers consisting of an antigenic peptide-spacer-beta(2)-microglobulin-spacer H chain. Our results indicate that these single-chain constructs assemble efficiently, maintain their covalent structure, and are unusually stable at the cell surface. Consequently, these constructs are at least 1000-fold less accessible to exogenous peptide than class I molecules loaded with endogenous peptides, and they are potent simulators of peptide-specific CTL and Abs. Our combined findings suggest that single-chain trimers may have applications as DNA vaccines against virus infection or tumors.
Yu
Yik Y L
YY
Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Netuschil
Nikolai
N
Lybarger
Lonnie
L
Connolly
Janet M
JM
Hansen
Ted H
TH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004527:Egg Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000276:immunology / Q000502:physiology; D006183:H-2 Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D007739:L Cells; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*; D001613:beta 2-Microglobulin / Q000138:chemical synthesis / Q000235:genetics / Q000502:physiology
D004527:Egg Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015395:Histocompatibility Antigens Class I; C110366:OVA-8; D010446:Peptide Fragments; D001613:beta 2-Microglobulin; D010047:Ovalbumin