Identification of a broad coverage HLA-DR degenerate epitope pool derived from carcinoembryonic antigen.
CD4 T cells are important for anti-tumor immune responses. Aside from their role in the activation of CD8 T cells, CD4 T cells also mediate anti-tumor immune responses by recruiting innate immune effectors into the tumor microenvironment. Thus, the search for strategies to boost CD4 T cell immunity is an active area of research. Our goal in this study was to identify HLA-DR epitopes of carcinoembryonic antigen (CEA), a commonly over-expressed tumor antigen. HLA-DR epitopes of CEA were identified using the epitope prediction program, PIC (predicted IC(50)) and tested using in vitro HLA-DR binding assays. Following CEA epitope confirmation, IFN-gamma ELIspot assays were used to detect existing immunity against the HLA-DR epitope panel of CEA in breast and ovarian cancer patients. In vitro generated peptide-specific CD4 T cells were used to determine whether the epitopes are naturally processed from CEA protein. Forty-three epitopes of CEA were predicted, 15 of which had high binding affinity for 8 or more common HLA-DR molecules. A degenerate pool of four, HLA-DR restricted 15 amino acid epitopes (CEA.24, CEA.176/354, CEA.488, and CEA.653) consisting of two novel epitopes (CEA.24 and CEA.488) was identified against which 40% of breast and ovarian cancer patients had pre-existent T cell immunity. All four epitopes are naturally processed by antigen-presenting cells. Hardy-Weinberg analysis showed that the pool is useful in approximately 94% of patients. Patients with breast or ovarian cancer demonstrate pre-existent immune responses to the tumor antigen CEA. The degenerate pool of CEA peptides may be useful for augmenting CD4 T cell immunity.
Karyampudi
Lavakumar
L
Department of Immunology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Krco
Christopher J
CJ
Kalli
Kimberly R
KR
Erskine
Courtney L
CL
Hartmann
Lynn C
LC
Goodman
Karin
K
Ingle
James N
JN
Maurer
Matthew J
MJ
Nassar
Aziza
A
Yu
Chao
C
Disis
Mary L
ML
Wettstein
Peter J
PJ
Fikes
John D
JD
Beebe
Melanie
M
Ishioka
Glenn
G
Knutson
Keith L
KL
D000328:Adult; D001943:Breast Neoplasms / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D000939:Epitopes; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology; D012984:Software
D002272:Carcinoembryonic Antigen; D000939:Epitopes; D006684:HLA-DR Antigens