An HLA-DR-degenerate epitope pool detects insulin-like growth factor binding protein 2-specific immunity in patients with cancer

Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I-based vaccines. In this study, the goal was to identify an HLA-DR-degen...

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Published in:	Cancer research (Chicago, Ill.) Vol. 68; no. 12; pp. 4893 - 4901
Main Authors:	Kalli, Kimberly R, Krco, Christopher J, Hartmann, Lynn C, Goodman, Karin, Maurer, Matthew J, Yu, Chao, Johnson, Elliot M, Erskine, Courtney L, Disis, Mary L, Wettstein, Peter J, Fikes, John D, Beebe, Melanie, Ishioka, Glenn, Knutson, Keith L
Format:	Journal Article
Language:	English
Published:	United States 15-06-2008
Subjects:	Adult Case-Control Studies CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Dendritic Cells - immunology Enzyme-Linked Immunosorbent Assay Epitopes HLA-DR1 Antigen - genetics HLA-DR1 Antigen - immunology Humans Insulin-Like Growth Factor Binding Protein 2 - immunology Insulin-Like Growth Factor Binding Protein 2 - metabolism Neoplasms - immunology Peptide Fragments - immunology Peptide Fragments - metabolism
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Summary:	Recent studies have shown the importance of helper CD4 T cells in initiating and sustaining tumor-specific CD8 T-cell immunity. This has paved the way for identifying MHC class II epitopes that could be incorporated into class I-based vaccines. In this study, the goal was to identify an HLA-DR-degenerate epitope pool derived from insulin-like growth factor binding protein 2 (IGFBP-2). IGFBP-2, a regulator of insulin-like growth factor action, is overexpressed in the majority of breast and ovarian cancers. Using algorithms, we predicted 29 HLA-DR1-binding epitopes. Binding assays targeting 15 different HLA-DRs revealed that 10 epitopes were degenerate, binding to at least four different HLA-DR variants. An IFN-gamma enzyme-linked immunosorbent spot assay was used to assess immunity to these 10 epitopes in 48 patients with either breast or ovarian cancer and 18 controls. Elevated T-cell immunity in patients was detected in 4 of the 10 epitopes (IGFBP2.17, IGFBP2.22, IGFBP2.249, and IGFBP2.293). The cumulative T-cell frequency of these four epitopes was elevated in patients relative to controls. All four peptides are naturally processed and presented to CD4 T-cells. The degenerate pool of peptides covers nearly 80% of patients and may be useful for augmenting CD4 T-cell immunity in patients undergoing immunization.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 G. Ishioka and K.L. Knutson: co-senior authors. Note: K.R. Kalli and C.J. Krco: co-first authors.
ISSN:	0008-5472 1538-7445
DOI:	10.1158/0008-5472.CAN-07-6726