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
✍ Scribed by Takahiro Gyotoku; Yoshinori Fukui; Takehiko Sasazuki
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 242 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
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 E § peptide (E § 52-68), a major self determinant bound to I-A b molecules, elicits an immune response in E § -transgenic C57BL/6 (E § -B6) mice where E § 52-68 is endogenously processed and presented by I-A b molecules in the thymus and periphery. To better understand this response, a panel of T cell hybridomas raised against exogenous E § 52-68 were analyzed for their reactivity to spleen cells from E § -B6 mice. Some hybridomas were stimulated with E § -B6 spleen cells in the absence of exogenous E § 52-68, whereas others were not stimulated with them. The E § 52-68/I-A b complex recognized by the TCR that is expressed on the hybridoma with reactivity to E § -B6 spleen cells was found to be quite stable, whereas the complex recognized by the TCR on the hybridoma specific for the exogenous E § 52-68 lost the stimulation activity by incubation the complex at 37 °C for 10 min. Stimulation experiments using extensively substituted E § analogue peptides suggested that amino acid residues at positions 57, 58, 60 and 62 of E § 52-68 are involved in the interaction with TCR recognizing the E § 52-68/ I-A b complex expressed on E § -B6 spleen cells. While amino acid substitutions at positions 60 and 62 also affected the recognition of TCR specific for exogenous E § 52-68, 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.