Limits...
Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.

Wang RF, Appella E, Kawakami Y, Kang X, Rosenberg SA - J. Exp. Med. (1996)

Bottom Line: This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration.Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide.Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

View Article: PubMed Central - PubMed

Affiliation: National Cancer Institute, Bethesda, Maryland 20892, USA.

ABSTRACT
The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

Show MeSH

Related in: MedlinePlus

Identification of TRP-2 as a tumor antigen recognized by  CTL clone 4. GM-CSF release by CTL clone 4 was measured after coculture with COS-7 cotransfected with the HLA-A31 cDNA along with  genes encoding MART-1, gp75/TRP-1, gp100, tyrosinase, p15, and  TRP-2. Control stimulator cells included 586mel, 397mel, COS-7 alone,  and COS-7 transfected with the HLA-A31 cDNA.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211562&req=5

Figure 2: Identification of TRP-2 as a tumor antigen recognized by CTL clone 4. GM-CSF release by CTL clone 4 was measured after coculture with COS-7 cotransfected with the HLA-A31 cDNA along with genes encoding MART-1, gp75/TRP-1, gp100, tyrosinase, p15, and TRP-2. Control stimulator cells included 586mel, 397mel, COS-7 alone, and COS-7 transfected with the HLA-A31 cDNA.

Mentions: Since only a limited number of T cells were available, we first tested whether or not these T cells recognized previously identified tumor antigens or melanocyte-lineage differentiation proteins. Recognition of COS-7 cells transfected with HLA-A31 cDNA and genes encoding the known tumor antigens or putative antigens including MART-1 (13), gp75 (18), gp100 (15), tyrosinase (17), p15 (26), and TRP-2 (25, 27) by CTL clone 4 was tested. COS cells transfected with HLA-A31 alone or TRP-2 alone did not confer recognition by the T cell clones. However, COS cells transfected with HLA-A31 and TRP-2 cDNA stimulated GMCSF release from T cells, whereas COS cells transfected with HLA-A31 and other genes did not, indicating that the T cell clone 4 recognized TRP-2 as a tumor antigen in an HLA-A31 restricted manner (Table 1 and Fig. 2). TRP-2 is located on the human chromosome 13 and has been shown to be a member of the tyrosinase-related gene family and shares a 40–45% amino acid sequence identity with tyrosinase and gp75/TRP-1 (25, 27). TRP-2 encodes a protein with 519 amino acids and has been demonstrated to have DOPAchrome tautomerase activity involved in melanin synthesis (27).


Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes.

Wang RF, Appella E, Kawakami Y, Kang X, Rosenberg SA - J. Exp. Med. (1996)

Identification of TRP-2 as a tumor antigen recognized by  CTL clone 4. GM-CSF release by CTL clone 4 was measured after coculture with COS-7 cotransfected with the HLA-A31 cDNA along with  genes encoding MART-1, gp75/TRP-1, gp100, tyrosinase, p15, and  TRP-2. Control stimulator cells included 586mel, 397mel, COS-7 alone,  and COS-7 transfected with the HLA-A31 cDNA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211562&req=5

Figure 2: Identification of TRP-2 as a tumor antigen recognized by CTL clone 4. GM-CSF release by CTL clone 4 was measured after coculture with COS-7 cotransfected with the HLA-A31 cDNA along with genes encoding MART-1, gp75/TRP-1, gp100, tyrosinase, p15, and TRP-2. Control stimulator cells included 586mel, 397mel, COS-7 alone, and COS-7 transfected with the HLA-A31 cDNA.
Mentions: Since only a limited number of T cells were available, we first tested whether or not these T cells recognized previously identified tumor antigens or melanocyte-lineage differentiation proteins. Recognition of COS-7 cells transfected with HLA-A31 cDNA and genes encoding the known tumor antigens or putative antigens including MART-1 (13), gp75 (18), gp100 (15), tyrosinase (17), p15 (26), and TRP-2 (25, 27) by CTL clone 4 was tested. COS cells transfected with HLA-A31 alone or TRP-2 alone did not confer recognition by the T cell clones. However, COS cells transfected with HLA-A31 and TRP-2 cDNA stimulated GMCSF release from T cells, whereas COS cells transfected with HLA-A31 and other genes did not, indicating that the T cell clone 4 recognized TRP-2 as a tumor antigen in an HLA-A31 restricted manner (Table 1 and Fig. 2). TRP-2 is located on the human chromosome 13 and has been shown to be a member of the tyrosinase-related gene family and shares a 40–45% amino acid sequence identity with tyrosinase and gp75/TRP-1 (25, 27). TRP-2 encodes a protein with 519 amino acids and has been demonstrated to have DOPAchrome tautomerase activity involved in melanin synthesis (27).

Bottom Line: This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration.Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide.Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

View Article: PubMed Central - PubMed

Affiliation: National Cancer Institute, Bethesda, Maryland 20892, USA.

ABSTRACT
The infusion of TIL586 along with interleukin-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. Here we report that TRP-2 was identified as a second tumor antigen recognized by a HLA-A31-restricted CTL clone derived from the TIL586 cell line. The peptide LLPGGRPYR epitope was subsequently identified from the coding region of TRP-2 based on studies of the recognition of truncated TRP-2 cDNAs and the HLA-A31 binding motif. This epitope peptide was capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Although some modified peptides could be recognized by the CTL clone, none were found to be better recognized by T cells than the parental peptide. Like other melamona differentiation antigens, TRP-2 was only expressed in melanoma, melanocytes, and retina, but not in other human tissues tested.

Show MeSH
Related in: MedlinePlus