OVERCOMING THE CRYPTICITY OF A VIRAL T-CELL DETERMINANT BY INSERTION INTO A CHIMERIC BACTERIAL PROTEIN

Among the potential T cell determinants contained in a protein antigen , the T cell response only focuses on a few immunodominant T cell dete rminants, whereas cryptic epitopes remain hidden to the immune system, In the present work, we have studied the antigen processing and prese ntation of the C3:93-115 sequence of Mahoney poliovirus VP1 protein, w hich is immunodominant in H-2(d) but cryptic in H-2(s) and H-2(q) mous e MHC haplotypes, For this purpose, we genetically inserted the C3 det erminant into five internal sites of a bacterial protein, the maltose binding protein of Escherichia coil (MalE), In four out of five insert ion sites of MalE, the C3 determinant retained its immunodominance whe n the purified hybrid proteins were injected to BALB/c (H-2(d)) mice, Moreover, in SJL/J (H-2(s)) mice, in three out of five MalE-C3 constru cts, the new structural environment of the cryptic C3 epitope rescued its processing and its in vivo presentation to T cells, In contrast, i n DBA/1 (H-2(q)) mice, although MalE-C3 chimeric proteins were correct ly processed in vitro, the C3 epitope remained cryptic in vivo, In thi s case, the impairment to stimulate a T cell response in vivo was corr elated with a short time persistence of C3 peptides bound to A(q) mole cules at the surface of live antigen-presenting cells, These results e mphasize the role of flanking residues on the lack of processing of cr yptic determinants and the importance of the life span of peptide-MHC complexes to stimulate T cell responses.