Interaction of an immunodominant epitope with Ia molecules in T-cell activation

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L Adorini, A Sette, S Buus, H M Grey, M Darsley, P V Lehmann, G Doria, Z A Nagy, E Appella

The amino acid sequence corresponding to residues 107-116 of hen egg-white lysozyme (HEL) has been identified as containing an immunodominant T-cell epitope recognized in association with the I-Ed molecule. The immunodominance of this epitope in HEL-primed H-2d mice was demonstrated by analysis of the T-cell proliferative response induced by synthetic peptides covering almost the entire HEL sequence. All the T-cell hybridomas from H-2d mice analyzed recognize the HEL sequence 107-116 in association with the I-Ed molecule. Correlating with the restriction of T-cell recognition, HEL-(105-120)-peptide binds to I-Ed but not to I-Ad molecules. Conservative or semiconservative substitutions at positions 113 (Asn----Lys), 114 (Arg----His), or 115 (Cys----Ala) abrogate the ability of HEL-(105-120) to activate T cells. Substitutions at residues 113 and 115 affect T-cell recognition but not the binding to I-Ed molecules, whereas, as shown by binding data and competition experiments, an Arg----His substitution at position 114 profoundly impairs the capacity of the peptide to interact with I-Ed molecules. In agreement with these results, [Lys113]HEL-(105-120)-peptide but not [His114]HEL-(105-120)-peptide was found to be immunogenic in H-2d mice. Thus, a single semiconservative substitution drastically reduces binding capacity and abolishes immunogenicity, suggesting that a strict correlation exists between binding of a peptide to Ia molecules and its immunogenicity.
Original languageEnglish
JournalProceedings of the National Academy of Science of the United States of America
Volume85
Issue number14
Pages (from-to)5181-5
Number of pages4
ISSN0027-8424
Publication statusPublished - 1988

Bibliographical note

Keywords: Amino Acid Sequence; Animals; Binding, Competitive; Chickens; Epitopes; Female; Freund's Adjuvant; H-2 Antigens; Histocompatibility Antigens Class II; Hybridomas; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Molecular Sequence Data; Muramidase; Structure-Activity Relationship; T-Lymphocytes

ID: 9947573