MHC-peptide binding: Dimers of cysteine-containing nonapeptides bind with high affinity to HLA-A2.1 Class I molecules

Francesca Di Modugno, Caterina Mammi, Laura Rosanò, Oriana Rubiu, Paola Nisticò, Alberto Chersi

Research output: Contribution to journalArticle

Abstract

Small peptides, 8-10 aminoacids long, derived from degradation of cytoplasmic proteins by a proteasome-proteinase complex, are usually presented and recognized by CD8+ cytolytic T lymphocytes (CTLs) associated with major histocompatibility complex (MHC) class I molecules. Recently synthetic peptides were used for the in vitro induction of tumor-specific CTLs, offering another strategy in the study of the immune-response repertoire and providing a new tool in cancer vaccination and immunotherapy. Peptides derived from otherwise normal proteins, overexpressed in many tumors as products of the protooncogene, may represent a target for an immune response. This is the case of HER-2/neu gene (also known as ErbB-2), encoding a cysteine-rich glycoprotein transmembrane receptor with tyrosine kinase activity (gp185neu). Recent data, demonstrating that HLA-A2.1.-related peptides are able to stimulate in vitro CD8+ lymphocytes, prompted us to study the binding to HLA-A2.1 molecules of several gp185 synthetic peptides containing a cystein residue and to define the relevance of this amino acid residue in the reduced or oxidated form of the sulfhydryl group. We found that monomers and their homodimers, linked by a disulfide bridge, bind to HLA-A2.1 molecules with overlapping affinity. These results suggest that additional amino acids of the nonapeptide do not prevent the binding and the HLA refolding through chemical or sterical interactions. This might be of particular relevance for the in vivo processing of cysteine-rich proteins. Because ErbB-2 molecules, as tumor-differentiation antigens in melanoma, are cysteine-rich molecules, it may be relevant to evaluate the possible role of the cystine residues interacting with the T-cell receptor. The recognition of these heretodimers by CD8+ lymphocytes will require functional in vivo studies.

Original languageEnglish
Pages (from-to)431-436
Number of pages6
JournalJournal of Immunotherapy
Volume20
Issue number6
Publication statusPublished - 1997

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Keywords

  • Cysteine
  • Cystine
  • ErbB-2
  • HLA-A2.1
  • Peptides

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Immunology

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