A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor

Eugene Y. Chiang, Iwona Stroynowski

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Although CTL and polymorphic, classical MHC class I molecules have well defined roles in the immune response against tumors, little is currently known regarding the participation of nonpolymorphic, nonclassical MHC class I in antitumor immunity. Using an MHC class I-deficient melanoma as a model tumor, we demonstrate that Q9, a murine MHC class Ib molecule from the Qa-2 family, expressed on the surface of tumor cells, protects syngeneic hosts from melanoma outgrowth. Q9-mediated protective immunity is lost or greatly diminished in mice deficient in CTL, including β2-microglobulin knockout (KO), CD8 KO, and SCID mice. In contrast, the Q9 antitumor effects are not detectably suppressed in CD4 KO mice with decreased Th cell activity. Killing by antitumor CTL in vitro is Q9 specific and can be blocked by anti-Q9 and anti-CD8 Abs. The adaptive Q9-restricted CTL response leads to immunological memory, because mice that resist the initial tumor challenge reject subsequent challenges with less immunogenic tumor variants and show expansion of CD8+ T cell populations with an activated/memory CD44high phenotype. Collectively, these studies demonstrate that a MHC class Ib molecule can serve as a restriction element for antitumor CTL and mediate protective immune responses in a syngeneic setting.

Original languageEnglish (US)
Pages (from-to)4394-4401
Number of pages8
JournalJournal of Immunology
Volume173
Issue number7
StatePublished - Oct 1 2004

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Melanoma
Neoplasms
Knockout Mice
Immunity
Immunologic Memory
SCID Mice
Rejection (Psychology)
T-Lymphocytes
Phenotype
Population

ASJC Scopus subject areas

  • Immunology

Cite this

A nonclassical MHC class I molecule restricts CTL-mediated rejection of a syngeneic melanoma tumor. / Chiang, Eugene Y.; Stroynowski, Iwona.

In: Journal of Immunology, Vol. 173, No. 7, 01.10.2004, p. 4394-4401.

Research output: Contribution to journalArticle

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abstract = "Although CTL and polymorphic, classical MHC class I molecules have well defined roles in the immune response against tumors, little is currently known regarding the participation of nonpolymorphic, nonclassical MHC class I in antitumor immunity. Using an MHC class I-deficient melanoma as a model tumor, we demonstrate that Q9, a murine MHC class Ib molecule from the Qa-2 family, expressed on the surface of tumor cells, protects syngeneic hosts from melanoma outgrowth. Q9-mediated protective immunity is lost or greatly diminished in mice deficient in CTL, including β2-microglobulin knockout (KO), CD8 KO, and SCID mice. In contrast, the Q9 antitumor effects are not detectably suppressed in CD4 KO mice with decreased Th cell activity. Killing by antitumor CTL in vitro is Q9 specific and can be blocked by anti-Q9 and anti-CD8 Abs. The adaptive Q9-restricted CTL response leads to immunological memory, because mice that resist the initial tumor challenge reject subsequent challenges with less immunogenic tumor variants and show expansion of CD8+ T cell populations with an activated/memory CD44high phenotype. Collectively, these studies demonstrate that a MHC class Ib molecule can serve as a restriction element for antitumor CTL and mediate protective immune responses in a syngeneic setting.",
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