Single amino acid changes in DR and antigen define residues critical for peptide-MHC binding and T cell recognition

Single amino acid substitutions of Ag and MHC were used to analyze the fine structure of the influenza hemagglutinin (HA)-derived epitope (HA 307-319) recognized in the context of DR7 molecules by a T cell clone. Putative T cell (HA 308, 310, 311, 313, and 316) and DR (HA 309, 312, and 317) contact...

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Bibliographic Details
Published in:	The Journal of immunology (1950) Vol. 146; no. 7; pp. 2331 - 2340
Main Authors:	Krieger, JI, Karr, RW, Grey, HM, Yu, WY, O'Sullivan, D, Batovsky, L, Zheng, ZL, Colon, SM, Gaeta, FC, Sidney, J
Format:	Journal Article
Language:	English
Published:	Bethesda, MD Am Assoc Immnol 01-04-1991 American Association of Immunologists
Subjects:	Amino Acid Sequence Antigen-Presenting Cells - immunology Antigens Antigens, Viral - immunology Binding Sites Biological and medical sciences Clone Cells Epitopes Fundamental and applied biological sciences. Psychology Fundamental immunology Hemagglutinins, Viral - immunology Histocompatibility antigens (hla, h-2 and other systems) HLA-DR Antigens - chemistry HLA-DR Antigens - metabolism Humans Immunity, Cellular In Vitro Techniques Major Histocompatibility Complex Molecular immunology Molecular Sequence Data Orthomyxoviridae - immunology Protein Conformation Structure-Activity Relationship T-Lymphocytes - immunology Human Antigen presentation Hemagglutinin HLA-DR-System Major histocompatibility system Class II histocompatibility antigen Molecular interaction In vitro Antigen Transfection Substitution Aminoacid Mutation Lymphocyte Recognition
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Summary:	Single amino acid substitutions of Ag and MHC were used to analyze the fine structure of the influenza hemagglutinin (HA)-derived epitope (HA 307-319) recognized in the context of DR7 molecules by a T cell clone. Putative T cell (HA 308, 310, 311, 313, and 316) and DR (HA 309, 312, and 317) contact residues of the Ag were identified by the use of single amino acid-substituted analogs that were tested for their T cell-activating and DR-binding capacities. The peptide-DR7-T cell interaction was further characterized by the use of a panel of 13 site-directed DR7 mutant transfectants analyzed for their capacity to present Ag to T cells, and for their purified mutant DR7 molecules to bind HA 307-319 or its single amino acid-substituted analogs. Eight mutants lost their Ag-presenting function, whereas only one had any decrease in peptide binding. Finally, for three of the mutants it was possible to correct the deleterious effects of mutation by using a particular single amino acid-substituted analog of the peptide molecule. The observed pattern of complementation led to a model that predicts that the Ag assumes an extended conformation, with a turn, in the binding groove, such that the following residues are in close proximity: DR 86-HA 309, DR 71-HA 312, DR 30-HA 314, and 315.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0022-1767 1550-6606
DOI:	10.4049/jimmunol.146.7.2331