Modulation of TCR recognition of MHC class II/peptide by processed remote N- and C-terminal epitope extensions.
N- and C-terminal extensions of naturally processed MHC class II-bound peptides may affect TCR recognition. In fact, residues immediately flanking the minimal epitope on either side can contact the MHC groove and modify the interaction with a TCR. We report now that residues much farther away from the peptide core can also modulate TCR recognition in a functional antigen presentation system. To show this, we isolated from the same donor DR5-restricted T cell clones, specific for the HIV-1 RT(248-262) sequence and differing in their ability to respond to recombinant antigens obtained by insertion of the epitope in different positions of schistosomal, human, or murine glutathione-S-transferase (GST). We found that the reactivity profile of individual clones was related to their TCR fine specificity, suggesting that processing can generate determinants focused onto the same epitope, but antigenically distinct. In addition, we analyzed the response of this panel of T-helper cell clones against GST-derived recombinant antigens in which the epitope was flanked by stretches of polyalanine or polyserine on either side. These spacers had different effects on TCR recognition suggesting that secondary structures outside the core peptide may influence MHC/epitope complex recognition over a distance of 15-30 residues from the determinant.
Bonomi
G
G
International Institute of Genetics and Biophysics, CNR, Naples, Italy. bonomi@iigbna.iigb.na.cnr.it
Moschella
F
F
Ombra
M N
MN
Del Pozzo
G
G
Granier
C
C
De Berardinis
P
P
Guardiola
J
J
D000595:Amino Acid Sequence; D000596:Amino Acids; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D010455:Peptides / Q000276:immunology*; D011499:Protein Processing, Post-Translational; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*
D000596:Amino Acids; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D005982:Glutathione Transferase; D054303:HIV Reverse Transcriptase