CARRIER-MEDIATED UPTAKE AND PRESENTATION OF A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED PEPTIDE

Citation
C. Brander et al., CARRIER-MEDIATED UPTAKE AND PRESENTATION OF A MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I-RESTRICTED PEPTIDE, European Journal of Immunology, 23(12), 1993, pp. 3217-3223
Citations number
53
Categorie Soggetti
Immunology
ISSN journal
00142980
Volume
23
Issue
12
Year of publication
1993
Pages
3217 - 3223
Database
ISI
SICI code
0014-2980(1993)23:12<3217:CUAPOA>2.0.ZU;2-K
Abstract
Antigenic peptides derived from endogenous or viral proteins can assoc iate with class I or class II major histocompatibility complex (MHC) m olecules, while exogenous antigens are endocytosed, processed intracel lularly and presented on MHC class II molecules. Here we describe a me thod that allows the presentation of an MHC class I-restricted antigen ic peptide on MHC class I molecules, although it was taken up from the outside. The HLA-A2-restricted influenza virus matrix protein-derived peptide (flu, 57-68) was used either in soluble form or coupled via a n S-S bridge to transferrin (Tf-flu). Target cells were incubated with flu or Tf-flu and the effective antigen presentation was detected in a cytotoxicity assay using flu peptide-specific, HLA-A2-restricted CD8 + cytotoxic T lymphocytes. Sensitization of target cells with Tf-flu r equired 5 to 10 times higher molar concentrations of peptide compared to sensitization with soluble free peptide. The Tf-flu construct was t aken up by the cells via the Tf receptor (CD71) as the binding of Tf-f lu was blocked by an excess of Tf. In contrast to the flu peptide, cyt otoxicity elicited by Tf-flu was blocked by brefeldin A but not by chl oroquine nor inhibitors of intracellular reducing steps, like 1-buthio nine-(s,r)-sulfoximine or n-ethylmaleimide. Presentation of the flu pe ptide derived from Tf-flu construct is not hindered in the mutant T2 c ell line, which lacks genes coding for transporter proteins for antige nic peptides (TAP1/TAP2) and proteasomes subunits, suggesting that the processing pathway described in this report may involve TAP-independe nt steps.