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-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.
Kalli
Kimberly R
KR
Departments of Oncology, Immunology, and Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.
Krco
Christopher J
CJ
Hartmann
Lynn C
LC
Goodman
Karin
K
Maurer
Matthew J
MJ
Yu
Chao
C
Johnson
Elliot M
EM
Erskine
Courtney L
CL
Disis
Mary L
ML
Wettstein
Peter J
PJ
Fikes
John D
JD
Beebe
Melanie
M
Ishioka
Glenn
G
Knutson
Keith L
KL
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016022:Case-Control Studies; D003713:Dendritic Cells / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D015798:HLA-DR1 Antigen / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism
D000939:Epitopes; D015798:HLA-DR1 Antigen; D018971:Insulin-Like Growth Factor Binding Protein 2; D010446:Peptide Fragments