Two tyrosinase nonapeptides recognized on HLA‐A2 melanomas by autologous cytolytic T lymphocytes

Abstract

A number of cytolytic T lymphocyte (CTL) clones derived from several melanoma patients have been found to recognize a majority of melanomas from HLA-A2 patients. We have reported previously that two such CTL clones recognize a product of the tyrosinase gene that is presented by HLA-A2. Here we show that one of these CTL clones recognizes a peptide encoded by the first nine amino acids of the putative signal sequence of tyrosinase. The other CTL clone recognizes a different tyrosinase peptide corresponding to amino acids 368-376. Both peptides contain consensus motifs of HLA-A2 binding peptides.

Factors Controlling the Trafficking and Processing of a Leader-Derived Peptide Presented by Qa-1

“…Class I-presented leader-derived peptides have been identified in both viral and tumor proteins (32,61). The study of their processing may help in understanding the generation of anti-viral and anti-tumor responses.…”

Novel antibodies as anticancer agents

“…Among this group, many specific antigens were identified, such as NY-ESO-1 and the MAGE-1 antigens, which belong to cancer-testis family, gp100, which belongs to the differentiation antigens group, and many more (Visseren et al, 1997;Chen et al, 1998a, b;Jager et al, 1998;Pascolo et al, 2001). It is well-established that human melanoma cells express antigens that are recognized by cytotoxic T-lymphocyte (CTL) derived from cancer patients (Brichard et al, 1993;Kawakami et al, 1994;Wolfel et al, 1994;Fleischhauer et al, 1996;Pittet et al, 1999;Kawakami et al, 2000;Engelhard et al, 2002;Romero et al, 2002;Schaed et al, 2002). These are mainly differentiation antigens such as gp100, MART1 and tyrosinase, which represent a very attractive target because their expression is limited to a well-defined cell lineage (melanocytes).…”

Comparison of recombinant adenovirus and synthetic peptide for DC-based melanoma vaccination

“…1,2 These melanoma antigens include normal cellular proteins such as the tyrosinase family of enzymes involved in melanin synthesis, which are endogenously expressed in melanocytes and melanoma cells. 3,4 However, it has become clear that mechanisms maintaining peripheral tolerance to melanocytic selfantigens present a major obstacle for the development of antigen-specific melanoma vaccines. [5][6][7] A number of strategies have been suggested to circumvent tolerance and induce effective antimelanoma immunity such as the adjuvant use of cultured dendritic cells (DC) or the coadministration of immunoenhancing molecules.…”