title: T lymphocyte recognition of peptide antigens: evidence favoring the formation of neoantigenic determinants.
abstract: To more precisely define the nature of exogenous antigenic determinants recognized by T cells, the response to fibrinopeptide fragment B beta 7-14 and a peptide of the inverted amino acid sequence of B beta 7-14 was examined. Strain 2 guinea pig T cells immunized with B beta 7-14 showed in vitro proliferative responses with B beta 7-14, but failed to respond to the inverted B beta 7-14 peptide. Moreover, the inverted B beta 7-14 peptide was nonimmunogenic and failed to prime strain 2 T cells for responses to native or inverted B beta 7-14. These results suggest that T cell recognition of peptide antigens involves more than simple interactions with amino acid side chains and that the ordering of the amino acids within the peptide is critical. One interpretation of these results is that T cells exhibit polarity in reading of antigenic determinants and peptides become associated with self in some fashion to form a neoantigenic determinant. To test this possibility, a Gly residue was added to the carboxyl end of B beta 7-14 (B beta 7-15), which is the likely site of attachment to self. It was found that strain 13 guinea pigs, which are totally unresponsive to B beta 7-14, produced T cell responses to B beta 7-15. This observation is consistent with the interpretation that Gly spaces the B beta 7-14 away from self to form an antigenic determinant complementary to strain 13 T cell antigen recognition structures. These results are discussed with respect to several mechanisms for immune response gene control of T cell responses.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D005338:Fibrin Fibrinogen Degradation Products / Q000276:immunology; D006168:Guinea Pigs; D010455:Peptides / Q000276:immunology*; D011487:Protein Conformation; D011948:Receptors, Antigen, T-Cell
chemical_list: D000939:Epitopes; D005338:Fibrin Fibrinogen Degradation Products; D010455:Peptides; D011948:Receptors, Antigen, T-Cell