Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1

Christopher E. Touloukian, Wolfgang W. Leitner, Rhonda E. Schnur, Paul F. Robbins, Yong Li, Scott Southwood, Alessandro Sette, Steven A. Rosenberg, Nicholas P. Restifo

Research output: Contribution to journalArticle

Abstract

Antitumor T cells often recognize targets that are nonmutated "self" tissue differentiation Ags, but the relative impact of Ag expression by normal and transformed tissue for a human self/tumor Ag has not been studied. To examine the influence of self-tolerance mechanisms on the function of self/tumor-specific T cell responses in humans, we sought to identify an Ag that was expressed, processed, and presented in an MHC-restricted fashion by tumor cells, but for which there was the human equivalent of a "knockout." In this study, We report the first immunological characterization of a melanoma/melanocyte differentiation Ag, called OA1, which meets these criteria. This Ag, an X chromosome-encoded melanoma/melanocyte differentiation Ag, was completely deleted in a male patient. Using a newly identified HLA-A*2402-restricted epitope (LYSACFWWL) to study T cell tolerance, we found that OA1-specific T cell reactivity was more than five SD higher in the knockout patient that in normal controls. These data provide compelling evidence for T cell tolerance to OA1 in humans. Most surprisingly, we found elevated levels of OA1-specific T cells in patients with metastatic malignant melanoma, indicating that the tumor-bearing state partially reversed tolerance observed in normal (non-"knockout") individuals. Taken together, these findings indicated that tolerance can exist for self/tumor Ags in humans, and that this tolerance could be partially abrogated by the growth of the tumor, increasing the reactivity of tumor Ag-specific T cells. Thus, the tumor-bearing state reverses, in part, the tolerance of T cells that results from the normal expression of tissue differentiation Ags.

Original languageEnglish (US)
Pages (from-to)1579-1585
Number of pages7
JournalJournal of Immunology
Volume170
Issue number3
StatePublished - Feb 1 2003
Externally publishedYes

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Melanoma-Specific Antigens
Neoplasm Antigens
T-Lymphocytes
Neoplasms
Melanoma
Melanocytes
Self Tolerance
HLA-A Antigens
X Chromosome
Epitopes

ASJC Scopus subject areas

  • Immunology

Cite this

Touloukian, C. E., Leitner, W. W., Schnur, R. E., Robbins, P. F., Li, Y., Southwood, S., ... Restifo, N. P. (2003). Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. Journal of Immunology, 170(3), 1579-1585.

Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. / Touloukian, Christopher E.; Leitner, Wolfgang W.; Schnur, Rhonda E.; Robbins, Paul F.; Li, Yong; Southwood, Scott; Sette, Alessandro; Rosenberg, Steven A.; Restifo, Nicholas P.

In: Journal of Immunology, Vol. 170, No. 3, 01.02.2003, p. 1579-1585.

Research output: Contribution to journalArticle

Touloukian, CE, Leitner, WW, Schnur, RE, Robbins, PF, Li, Y, Southwood, S, Sette, A, Rosenberg, SA & Restifo, NP 2003, 'Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1', Journal of Immunology, vol. 170, no. 3, pp. 1579-1585.
Touloukian CE, Leitner WW, Schnur RE, Robbins PF, Li Y, Southwood S et al. Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. Journal of Immunology. 2003 Feb 1;170(3):1579-1585.
Touloukian, Christopher E. ; Leitner, Wolfgang W. ; Schnur, Rhonda E. ; Robbins, Paul F. ; Li, Yong ; Southwood, Scott ; Sette, Alessandro ; Rosenberg, Steven A. ; Restifo, Nicholas P. / Normal tissue depresses while tumor tissue enhances human T cell responses in vivo to a novel self/tumor melanoma antigen, OA1. In: Journal of Immunology. 2003 ; Vol. 170, No. 3. pp. 1579-1585.
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AU - Li, Yong

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