Absence of γ-interferon-inducible lysosomal thiol reductase in melanomas disrupts T cell recognition of select immunodominant epitopes

M. Azizul Haque, Ping Li, Sheila K. Jackson, Hassane M. Zarour, John W. Hawes, Uyen T. Phan, Maja Maric, Peter Cresswell, Janice S. Blum

Research output: Contribution to journalArticle

97 Scopus citations

Abstract

Long-lasting tumor immunity requires functional mobilization of CD8+ and CD4+ T lymphocytes. CD4+ T cell activation is enhanced by presentation of shed tumor antigens by professional antigen-presenting cells (APCs), coupled with display of similar antigenic epitopes by major histocompatibility complex class II on malignant cells. APCs readily processed and presented several self-antigens, yet T cell responses to these proteins were absent or reduced in the context of class II+ melanomas. T cell recognition of select exogenous and endogenous epitopes was dependent on tumor cell expression of γ-interferon-inducible lysosomal thiol reductase (GILT). The absence of GILT in melanomas altered antigen processing and the hierarchy of immunodominant epitope presentation. Mass spectral analysis also revealed GILT's ability to reduce cysteinylated epitopes. Such disparities in the profile of antigenic epitopes displayed by tumors and bystander APCs may contribute to tumor cell survival in the face of immunological defenses.

Original languageEnglish (US)
Pages (from-to)1267-1277
Number of pages11
JournalJournal of Experimental Medicine
Volume195
Issue number10
DOIs
StatePublished - May 20 2002

Keywords

  • Cysteinylation
  • GILT
  • Immunodominance
  • Melanomas
  • MHC class II molecules

ASJC Scopus subject areas

  • Immunology

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