Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth

Eugene Y. Chiang, Maile Henson, Iwona Stroynowski

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

One of the principal mechanisms of tumor immune evasion is alteration of class I MHC expression. We have identified defects contributing to down-regulation of class I MHC expression in the widely studied murine B16 melanoma and its variants B16F1, B16F10, BL6-2, BL6-8 and B78H1. Transcription of the nonclassical class I MHC genes Q8 and Q9 (Qa-2 Ags) has been switched off in the entire panel of melanoma lines, suggesting that this event occurred early during tumor progression. B78H1, unlike B16F1 and B16F10 sublines, is also selectively devoid of TAP2 and low molecular weight protein 7 as well as classical class I MHC Kb and Db transcripts. Cotransfection of B78H1 with TAP2 and class I H chain genes is sufficient to reconstitute surface expression of exogenously delivered class I MHC without concomitant re-expression of endogenous β2-microglobulin-associated class I. The serological absence of endogenous class Ia and Ib at the surface of TAP2-negative as well as TAP2-transfected B78H1 makes this system a suitable model for studying the properties of isolated class I proteins in tumors. We used this system to demonstrate that B78H1 cells genetically manipulated to re-express Q9 Ag have reduced tumor potential in syngeneic B6 mice compared with TAP2-transfected parental melanoma. Both NK cells and CTLs appear to collaborate in restraining growth of Q9-positive tumors. The results implicate Qa-2 in antitumor responses and illustrate the utility of the B78H1 system for identifying in vivo interactions between class I MHC molecules of interest and immune cells of innate and/or adaptive immunity.

Original languageEnglish (US)
Pages (from-to)4515-4523
Number of pages9
JournalJournal of Immunology
Volume170
Issue number9
StatePublished - May 1 2003

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Melanoma
Growth
Neoplasms
Tumor Escape
MHC Class I Genes
Experimental Melanomas
Adaptive Immunity
Innate Immunity
Natural Killer Cells
Proteins
Down-Regulation
Molecular Weight
MHC Ib Qa-2 antigen
Genes

ASJC Scopus subject areas

  • Immunology

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Correction of defects responsible for impaired Qa-2 class Ib MHC expression on melanoma cells protects mice from tumor growth. / Chiang, Eugene Y.; Henson, Maile; Stroynowski, Iwona.

In: Journal of Immunology, Vol. 170, No. 9, 01.05.2003, p. 4515-4523.

Research output: Contribution to journalArticle

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