Murine leukemia RL male 1 and sarcoma Meth A antigens recognized by cytotoxic T lymphocytes (CTL).

Abstract

Peptide elution and expression cloning methods have been used to identify T cell-recognized antigens for which no molecular information is available. We identified a unique tumor antigen peptide pRL1a, IPGLPLSL that is recognized by CTL on BALB/c RL male 1 leukemia by peptide elution. The sequence of the peptide corresponded to the normally untranslated 5' region of akt. Cytotoxicity was generated in BALB/c spleen cells by in vivo and in vitro sensitization with pRL1a peptide in the form of multiple antigen peptide (MAP), but not the original form. pRL1a MAP immunization had a significant growth-inhibitory effect. pRL1a MAP was mostly internalized into the endosomal compartment of antigen-presenting cells, leaked to the cytosol, and degraded, and the pRL1a peptide produced was presented through the MHC class I pathway. In vivo depletion of CD4 T cells from tumor-inoculated BALB/c mice caused RL male 1 regression. Overexpression of the RLakt molecule seemed to induce CD4 immunoregulatory cells, which resulted in progressive RL male 1 growth in BALB/c mice. In vivo administration of anti-CD25 mAb (PC61) caused regression of RL male 1, suggesting that CD4(+) CD25(+) immunoregulatory cells were involved in the tumor growth. Recently, we improved the sensitivity and the efficacy of T cell antigen cloning from cDNA expression libraries by using large- and small-scale ELISPOT assays. Using the IFN-gamma ELISPOT method, we obtained a cDNA clone S35 of 937 bp recognized by AT-1 CTL on BALB/c Meth A sarcoma. S35 was a part of the retinoic acid-regulated nuclear matrix-associated protein (ramp). AT-1 CTL recognized the peptide LGAEAIFRL, which was derived from a newly created open reading frame due to the exon 14 extension.

• Authors: Akiko Uenaka, Eiichi Nakayama
• Journal: Cancer science (Cancer Sci) Vol. 94 Issue 11 Pg. 931-6 (Nov 2003) ISSN: 1347-9032 [Print] England
• PMID: 14611667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Antigens, Neoplasm
• Histocompatibility Antigens
• Oligopeptides
• pRL1a protein, mouse
• tumor-associated transplantation antigen

Topics

• Animals
• Antigen-Presenting Cells
• Antigens, Neoplasm (immunology)
• Histocompatibility Antigens (immunology)
• Leukemia (immunology, prevention & control)
• Mice
• Oligopeptides (immunology)
• Sarcoma, Experimental (immunology, prevention & control)
• T-Lymphocytes (immunology)
• T-Lymphocytes, Cytotoxic (immunology)