A MAGE-1 peptide recognized on HLA-DR15 by CD4+ T cells

Abstract

Antigens encoded by MAGE genes and recognized by T cells are of interest for cancer immunotherapy because of their strict tumoral specificity and because they are shared by many tumors. Several MAGE‐1 peptide that are recognized by CD8+ cytolytic T lymphocytes have been used in therapeutic vaccination trials. To obtain anti‐tumor immune response, vaccines combining peptides recognized by CD8+ and peptides recognized by CD4+ T cells might be optimal. We focused therefore on the identification of MAGE peptides recognized by CD4+ T cells. We report here the identification of MAGE‐1 epitope EYVIKVSARVRF, which is presented to CD4+ T lymphocytes by HLA‐DR15. This HLA allele is present in 29 % of Asians and 17 % of Caucasians.

Identification of a naturally processed cyclin D1 T‐helper epitope by a novel combination of HLA class II targeting and differential mass spectrometry

“…The identification of CD4 + T cell epitopes of tumorassociated antigens has experienced much attention lately [1][2][3][4][5][6][7][8], as CD4 + T helper cells play an important role in orchestrating the effector function of anti-tumor T cells [1,3,9], even in the absence of CTL effector cells, by acting in an indirect, cytokine-dependent manner [10][11][12]. They can inhibit tumor angiogenesis via IFN-c [13] and counteract tumor progression via the induction of an antibody response [14].…”

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

“…Because of the polymorphism of HLA class II molecules, CD4 T cell epitopes are variable in humans. During the last decades, many tumor Ags have been shown to elicit CD4 T cell responses and many T CD4 cell epitopes have been identified (3)(4)(5)(6)(7)(8). Besides differences in their expression in normal and tumor tissues and in their level of dispensability, tumor Ags also differ in their ability to mount spontaneous specific CD4 T cell responses in cancer patients.…”

“…Already identified CD4 T cell epitopes in tumor Ags exhibit different immunological properties. Although some CD4 T cell epitopes are restricted to particular, albeit frequent, HLA class II allotypes (4,5), others are promiscuous and immunogenic in multiple donors (6)(7)(8). They also differ by the amplitude of the T cell response they generate.…”

A novel approach to identify antigens recognized by CD4 T cells using complement-opsonized bacteria expressing a cDNA library

“…After induction of protein synthesis by IPTG treatment, bacteria expressing MAGE-1 were incubated with different antigen-presenting cells that were subsequently used to stimulate an anti-MAGE-1 CD4 clone. 36 Dendritic cells were efficient antigen-presenting cells but often stimulated nonspecifically the CD4 clone, as we experienced previously with several CD8 T cell clones in contact with dendritic cells and bacterial products. Moreover, large numbers of autologous human dendritic cells are usually not available.…”

“…The culture conditions of the MAGE-1-specific HLA-DR15-restricted CD4 T cell clone were previously described. 36 Cloning of the full-length DBY gene and DBY minigenes Total RNA was isolated from the male patient-derived EBV-LCL with Trizol (Invitrogen, Carlsbad, CA, USA) according to the manufacturer's procedure. cDNA was synthesized from RNA using M-MLV BRL reverse transcriptase (Invitrogen) for 60 min at 371C.…”