An endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability

Takahiro Gyotoku, Yoshinori Fukui, Takehiko Sasazuki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Immunization with self peptides often elicits activation of CD4+ T cells in vivo. Although such peptides have been suggested to be derived from minor self determinants or self antigens sequestered from the immune system, we found that immunization with Eα peptide (Eα52-68), a major self determinant bound to I-Ab molecules, elicits an immune response in Eα-transgenic C57BL/6 (Eα-B6) mice where Eα52-68 is endogenously processed and presented by I-Ab molecules in the thymus and periphery. To better understand this response, a panel of T cell hybridomas raised against exogenous Eα52-68 were analyzed for their reactivity to spleen cells from Eα-B6 mice. Some hybridomas were stimulated with Eα-B6 spleen cells in the absence of exogenous Eα52-68, whereas others were not stimulated with them. The Eα52-68/I-Ab complex recognized by the TCR that is expressed on the hybridoma with reactivity to Eα-B6 spleen cells was found to be quite stable, whereas the complex recognized by the TCR on the hybridoma specific for the exogenous Eα52-68 lost the stimulation activity by incubation the complex at 37°C for 10 min. Stimulation experiments using extensively substituted Eα analogue peptides suggested that amino acid residues at positions 57, 58, 60 and 62 of Eα52-68 are involved in the interaction with TCR recognizing the Eα52-68/I-Ab complex expressed on Eα-B6 spleen cells. While amino acid substitutions at positions 60 and 62 also affected the recognition of TCR specific for exogenous Eα52-68, all or many amino acid substitutions were allowed at position 58 or 57, respectively, without impairing the TCR recognition. Taken together, these results suggest that endogenously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct TCR ligands with different kinetic stability and probably with different configuration.

Original languageEnglish
Pages (from-to)4050-4061
Number of pages12
JournalEuropean Journal of Immunology
Volume28
Issue number12
DOIs
Publication statusPublished - Dec 1998

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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