Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens.

Abstract

From the peripheral blood of the melanoma patient (AV), we derived cytolytic T lymphocyte (CTL) clones that lysed the autologous tumor line SK-MEL-29, but not autologous EBV-B cells, K562, and other tumor targets. By immunoselection experiments it was shown that the CTL clones recognized at least three different antigens on the autologous tumor cells. We demonstrate here that these melanoma antigens are presented to the CTL in association with HLA-A2. First, HLA-A2-reactive pregnancy sera as well as an mAb against HLA-A2 inhibited the CTL lysis. Second, immunoselected melanoma subclones that were resistant to lysis by CTL clones against the three antigens described were found to lack expression of HLA-A2. By sensitizing the patient's lymphocytes against an HLA-A2- melanoma clone, we established a new series of CTL clones recognizing autologous AV melanoma cells. However, efficient lysis was only seen when target cells were pretreated with IFN-gamma. The lytic activity of these CTL was selectively inhibited by an mAb against a common HLA-B determinant. These results indicate that in addition to HLA-A2, other class I antigens are involved in the recognition of AV melanoma cells by autologous CTL.

Recognition of neuroectodermal tumors by melanoma-specific cytotoxic T lymphocytes: evidence for antigen sharing by tumors derived from the neural crest

“…While TIL 1143 lysed all 3 Ewing's sarcomas, the multiple specificities of this polyclonal culture complicate interpretations of tumor antigen sharing. Individual melanoma lines have been shown to express multiple distinct tumor antigens recognized by specific CTL [21,22,27,29]. Thus, while our polyclonal TIL cultures are all capable of specifically recognizing the HLA-A2 + melanomas 501-mel, 624-mcl, and a variety of others, they do not necessarily react with a single tumor antigen.…”

“…Cytolytic T cells can recognize commonly expressed melanoma-associated antigens in the context of a variety of HLA-A, -B, and -C, molecules [5,6,9,10,17,28,29]. Such MHC-class-I-restricted T cells have also been shown to recognize cultured normal melanocytes [1], suggesting targeting of a differentiation antigen.…”

High-Affinity HLA-A(*)02.01 Peptides from Parathyroid Hormone-Related Protein Generate In Vitro and In Vivo Antitumor CTL Response Without Autoimmune Side Effects

“…C ytotoxic T lymphocytes recognize protein Ags as small peptide products of cytoplasmic proteolysis bound to MHC molecules (1,2). Epitope peptide binding to specific HLA isotypes is determined by definite consensus motifs present in the amino acid sequences of the Ag peptides (1)(2)(3)(4).…”

“…Epitope peptide binding to specific HLA isotypes is determined by definite consensus motifs present in the amino acid sequences of the Ag peptides (1)(2)(3)(4).…”

Dendritic Cells Infected with a Vaccinia Vector Carrying the Human gp100 Gene Simultaneously Present Multiple Specificities and Elicit High-Affinity T Cells Reactive to Multiple Epitopes and Restricted by HLA-A2 and -A3

“…Work by Kawakami et al (24) demonstrated the presence of multiple peptide specificities within therapeutic cytotoxic tumor-infiltrating lymphocytes, demonstrating the potential diversity of the in vivo CTL response against melanoma. In other studies, using T cell clones or Ag loss tumor variants, it has been established that multiple specificities exist in CTL lines induced in vitro after stimulation with tumor cells (31)(32)(33). Tüting et al (34), utilizing autologous DC transfected with one or multiple cDNAs encoding melanoma TAA to stimulate PBL from normal donors, demonstrated TAA peptide-specific CTL reactivity.…”