H2-M3 presents a nonformylated viral epitope to CTLs generated in vitro.
Most CTL responses to epitopes from influenza virus are restricted by MHC class Ia molecules. However, a synthetic peptide corresponding to residues 173 to 190 of influenza A/JAP/305/57 hemagglutinin (HA) can induce, in vitro, a CTL response to peptide presented by a mouse class Ib molecule encoded by a gene telomeric to H2-Q. Here, we identify the molecule as H2-M3 and show that the last five residues of HA173-190, MLIIW, is the minimal epitope for CTL recognition. Cells that express M3wt, from C57BL/6 or BALB/c mice, are sensitized by both MLIIW and the longer peptide HA173-190, whereas cells that express M3f, from A.CA or B10.M mice, are sensitized only by MLIIW; a single amino acid change at residue 31 (V-->M) of M3 accounts for this difference. Although M3-restricted CTLs preferably recognize N-formylated epitopes, i.e., those of mitochondrial or prokaryotic origin, our findings show that M3-restricted primary CTL responses can be generated in vitro against nonformylated epitopes.
Byers
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DE
Howard Hughes Medical Institute, Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
Fischer Lindahl
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D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D001667:Binding, Competitive / Q000276:immunology; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology* / Q000378:metabolism; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009239:N-Formylmethionine / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D010446:Peptide Fragments; D010455:Peptides; D009239:N-Formylmethionine