Interaction of an immunodominant epitope with Ia molecules in T-cell activation.
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.
Adorini
L
L
Laboratory of Pathology, ENEA, C.R.E. Casaccia, Rome, Italy.
Sette
A
A
Buus
S
S
Grey
H M
HM
Darsley
M
M
Lehmann
P V
PV
Doria
G
G
Nagy
Z A
ZA
Appella
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D002645:Chickens; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005620:Freund's Adjuvant; D006183:H-2 Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D009113:Muramidase / Q000276:immunology; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen; D005620:Freund's Adjuvant; D009113:Muramidase