Mutation of the α2 domain disulfide bridge of the class I molecule HLA-A*0201 Effect on maturation and peptide presentation

Robert J. Warburton, Masanori Matsui, Sarah L. Rowland-Jones, Maureen C. Gammon, Gil E. Katzenstein, Taiyin Wei, Michael Edidin, Hans J. Zweerink, Andrew J. McMichael, Jeffrey A. Frelinger

Research output: Contribution to journalArticle

Abstract

A combination of saturation and site-directed mutagenesis was utilized to disrupt the α2 domain disulfide bridge of HLA-A*0201. Mutation of cysteine 101 to a serine (C101S) or of cysteine 164 to alanine (C164A) decreased the rate of maturation of the heavy chain, the total amount of mature heavy chain within the cell, and the level of surface expression. Cells expressing these genes and loaded with a synthetic peptide derived from the influenza A matrix protein (58-66) were recognized poorly by HLA-A*0201-restricted, peptide-specific CTLs. Cells expressing mutant HLA-A*0201 loaded with a synthetic peptide derived from the HIV-1 pol protein (476-484) were not recognized by pol IV-9-specific CTLs. Mutant C164A cells infected with influenza virus were partially recognized by influenza matrix peptide-specific CTLs, while C101S cells were not lysed. Surprisingly, endogenous peptide loading of cells expressing mutant HLA-A*0201 using a minigene coding for either the influenza A matrix peptide 58-66, or HIV-1 pol peptide 476-484, resulted in efficient CTL recognition. This suggests different structural constraints for peptide binding in the endoplasmic reticulum during biosynthesis and for binding to exported molecules on the cells surface.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalHuman Immunology
Volume39
Issue number4
DOIs
StatePublished - Apr 1994

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Warburton, R. J., Matsui, M., Rowland-Jones, S. L., Gammon, M. C., Katzenstein, G. E., Wei, T., Edidin, M., Zweerink, H. J., McMichael, A. J., & Frelinger, J. A. (1994). Mutation of the α2 domain disulfide bridge of the class I molecule HLA-A*0201 Effect on maturation and peptide presentation. Human Immunology, 39(4), 261-271. https://doi.org/10.1016/0198-8859(94)90269-0