Protective immunity against disparate tumors is mediated by a nonpolymorphic MHC class I molecule

Eugene Y. Chiang, Iwona Stroynowski

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Current peptide-based immunotherapies for treatment of model cancers target tumor Ags bound by the classical MHC class I (class Ia) molecules. The extensive polymorphism of class Ia loci greatly limits the effectiveness of these approaches. We demonstrate in this study that the murine nonpolymorphic, nonclassical MHC class I (class Ib) molecule Q9 (Qa-2) promotes potent immune responses against multiple syngeneic tumors. We have previously shown that ectopic expression of Q9 on the surface of class Ia-negative B78H1 melanoma led to efficient CTL-mediated rejection of this tumor. In this study, we report that surface-expressed Q9 on 3LLA9F1 Lewis lung carcinoma and RMA T cell lymphoma also induces potent antitumor CTL responses. Importantly, CTL harvested from animals surviving the initial challenge with Q9-positive 3LLA9F1, RMA, or B78H1 tumors recognized and killed their cognate tumors as well as the other cancer lines. Furthermore, immunization with Q9-expressing 3LLA9F1 or RMA tumor cells established immunological memory that enhanced protection against subsequent challenge with a weakly immunogenic, Q9-bearing melanoma variant. Collectively, the generation of cross-reactive CTL capable of eliminating multiple disparate Q9-expressing tumors suggests that this nonpolymorphic MHC class I molecule serves as a restriction element for a shared tumor Ag(s) common to lung carcinoma, T cell lymphoma, and melanoma.

Original languageEnglish (US)
Pages (from-to)5367-5374
Number of pages8
JournalJournal of Immunology
Volume174
Issue number9
StatePublished - May 1 2005

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Immunity
Neoplasms
Melanoma
T-Cell Lymphoma
Immunologic Memory
Lewis Lung Carcinoma
Immunotherapy
Immunization
Carcinoma
Lung
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Protective immunity against disparate tumors is mediated by a nonpolymorphic MHC class I molecule. / Chiang, Eugene Y.; Stroynowski, Iwona.

In: Journal of Immunology, Vol. 174, No. 9, 01.05.2005, p. 5367-5374.

Research output: Contribution to journalArticle

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