Differential presentation of tumor antigen‐derived epitopes by MHC‐class I and antigen‐positive tumor cells

Abstract

SSX2 is a member of the family of cancer/testis antigens. The SSX2 derived peptide SSX2 [103][104][105][106][107][108][109][110][111] has been shown to be presented to cytotoxic T-lymphocytes (CTL) by Major-Histocompatibility (MHC) Class-I complexes after endogenous processing, more precisely by the allele HLA-A*0201. The HLA-A*0201-and SSX2-positive melanoma cell line SK-Mel-37 but not Me275 had been shown to elicit reactivity in SSX2 103-111 specific cytotoxic T-lymphocytes. To analyze the correlation between SSX2 103-111 presentation and T-cell stimulation, we intended to visualize presentation of SSX2 103-111 in these melanoma cell lines. Fab-antibodies were established from a human phage library with specificity for SSX2 103-111 /HLA-A*0201 complexes (but non-reactive with HLA-A*0201 or SSX2 103-111 alone) and used to visualize the presentation of SSX2 [103][104][105][106][107][108][109][110][111]

The SSX Family of Cancer‐Testis Antigens as Target Proteins for Tumor Therapy

“…This finding indicates that the same physiological mechanisms that lead to SSX expression in the testis may be ectopically reactivated in tumor tissues. Except for SSX6 and SSX10, expression of all SSX family members has been demonstrated in testis tissue (Table 1) [29, 73]. …”

A non-pathogenic live vector as an efficient delivery system in vaccine design for the prevention of HPV16 E7-overexpressing cancers

“…The tumor cells may express different levels of antigenic peptides loaded by class I MHC molecule. For example, a portion of TC-1 tumor cells may load either E6-or E7-derived antigenic peptides on their MHC class I molecule in vivo (Held et al, 2008). Thus, it is likely that some TC-1 tumor cells may not be lysed by CD8þ T cells generated from vaccination with a single antigen-encoding DNA vaccine, indicating the importance of broad immunity (Seo et al, 2009).…”

Fab antibodies capable of blocking T cells by competitive binding have the identical specificity but a higher affinity to the MHC-peptide-complex than the T cell receptor

“…Clone VIE1 derived from this selection has been described in detail previously [16]. A phagemide-library expressing a large non-immune, human Fab repertoire, containing 3.7 × 10 10 antibody fragments was used as described previously [17].…”

“…SSX2 103-111/HLA-A*0201-specific CTL clones were established as described [16]. Assays were performed in nitrocellulose-lined 96-well plates (MHAN 45, Millipore, Bedford, MA).…”