Murine leukemia RL1 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 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 antigenpresenting cells, leaked to the cytosol, and degraded, and the pRL1a peptide produced was presented through the MHC class I pathway. umor rejection antigens were first found on methylcholanthrene-induced fibrosarcomas in mice. [1][2][3][4][5] Immunization of syngeneic mice with a tumor was shown to render these mice resistant to successive challenge by the same tumor. Studies on adoptive transfer showed that the tumor rejection response is mediated by T cells.6, 7) CD8 T cells are predominantly responsible for rejection, while CD4 T cells are involved to various extents, depending on the tumor. It is generally accepted that CD4 T cells help CD8 CTL precursors (pCTL) to differentiate into effector cells. 8, 9) CD8 and CD4 T cells recognize the peptide derived from intracellular and extracellular proteins presented on major histocompatibility complex (MHC) class I and class II molecules, respectively.Radiation-induced leukemia and methylcholanthrene-induced sarcoma occur after long latency and have been used as model tumors of human malignancies. RL 1 is a radiation-induced leukemia 10) and Meth A is a methylcholanthrene-induced sarcoma in BALB/c mice.11) Both those tumors were established in 1963 by Lloyd J. Old and have been widely used for the study of tumor immunology in many laboratories. Here, we describe the identification of the antigens on RL 1 and Meth A recognized by CTL and the host immune responses to those antigens. Involvement of regulatory CD4 + CD25 + cells in tumor growth is also described.

Photodynamic therapy and anti-tumour immunity

“…PDT (but not surgical removal) induced immune recognition of the foreign GFP as a model tumour antigen. As additional tumour-rejection antigens are identified in mouse tumour cell lines 100 , a more rational approach can be taken to studying the factors that govern the relative strength of anti-tumour immune responses stimulated by PDT for different tumours and PDT regimens.…”

Peptide dendrimers

“…T-cell recognized antigens for which no molecular information is available, have been identified [141]. A unique tumor antigen peptide pRL1a, IPGLPLSL that is recognized by CTL on BALB/c RL male 1 leukemia has been identified by peptide elution.…”

Identification of a 17β-hydroxysteroid dehydrogenase type 12 pseudogene as the source of a highly restricted BALB/c Meth A tumor rejection peptide

“…Several unrelated, highly restricted, T-cell-defined TRA of the Meth A sarcoma have been identified. These include mutant p53, ribosomal L11 and retinoic acid-regulated nuclear matrix-associated protein ( ramp ) peptides [13–15]. Of the three, however, only p53 has had any significant translational value relative to the development and implementation of cancer vaccines and immunotherapy of human cancer.…”