IMMUNODOMINANCE DOES NOT RESULT FROM PEPTIDE COMPETITION FOR MHC CLASS-II PRESENTATION

Competition for binding to MHC class II molecules between processed pe ptides derived from a single protein Ag is considered an important par ameter leading to the presentation of a Limited set of peptides by APC s, We tested the relevance of this competition process in a model Ag, the MalE protein, by deleting T cell epitopes or by introducing a comp etitor T cell peptide, We identified in DBA/1 (I-A(q)) mice six immuno dominant T cell determinants in the MalE sequence, 89-95, 116-123, 198 -205, 211-219, 274-281, and 335-341, Synthetic peptides carrying these determinants were classified in three groups as weak, intermediate, o r strong I-A(q) binders in competition experiments with the PreS:T pep tide of hepatitis B surface Ag, In vivo, synthetic MalE peptides with weak and intermediate MHC binding capacity were inhibited in their cap acity to stimulate proliferative response in the presence of the PreS: T competitor peptide, whereas the strongest MHC binder was not. Striki ngly, the insertion of the potent competitor PreS:T peptide into the M alE sequence, as a single copy or as four copies, did not inhibit the proliferative response to the six immunodominant peptides of the recip ient protein. Moreover, deletion in the protein sequence disrupting ei ther the weak (198-205) or strong (335-341) MHC binding determinant of MalE did not modify the proliferative response to the remaining T cel l determinants as compared with wild-type MalE protein. Altogether, th ese results show that peptide competition for MHC binding may not repr esent the most important event in processes leading to immunodominance .