T cell responses to HLA-A*0201-restricted peptides derived from human alpha fetoprotein.
alpha fetoprotein (AFP)-derived peptide epitopes can be recognized by human T cells in the context of MHC class I. We determined the identity of AFP-derived peptides, presented in the context of HLA-A*0201, that could be recognized by the human (h) T cell repertoire. We screened 74 peptides and identified 3 new AFP epitopes, hAFP(137-145), hAFP(158-166), and hAFP(325-334), in addition to the previously reported hAFP(542-550.) Each possesses two anchor residues and stabilized HLA-A*0201 on T2 cells in a concentration-dependent class I binding assay. The peptides were stable for 2-4 h in an off-kinetics assay. Each peptide induced peptide-specific T cells in vitro from several normal HLA-A*0201 donors. Importantly, these hAFP peptide-specific T cells also were capable of recognizing HLA-A*0201(+)/AFP(+) tumor cells in both cytotoxicity assays and IFN-gamma enzyme-linked immunospot assays. The immunogenicity of each peptide was tested in vivo with HLA-A*0201/K(b)-transgenic mice. After immunization with each peptide emulsified in CFA, draining lymph node cells produced IFN-gamma on recognition of cells stably transfected with hAFP. Furthermore, AFP peptide-specific T cells could be identified in the spleens of mice immunized with dendritic cells transduced with an AFP-expressing adenovirus (AdVhAFP). Three of four AFP peptides could be identified by mass spectrometric analysis of surface peptides from an HLA-A*0201 human hepatocellular carcinoma (HCC) cell line. Thus, compelling immunological and physiochemical evidence is presented that at least four hAFP-derived epitopes are naturally processed and presented in the context of class I, are immunogenic, and represent potential targets for hepatocellular carcinoma immunotherapy.
Butterfield
L H
LH
Division of Surgical Oncology, Department of Chemistry and Biochemistry, University of California Los Angeles Medical Center, Los Angeles, CA 90095, USA.
Meng
W S
WS
Koh
A
A
Vollmer
C M
CM
Ribas
A
A
Dissette
V B
VB
Faull
K
K
Glaspy
J A
JA
McBride
W H
WH
Economou
J S
JS
D000256:Adenoviridae / Q000235:genetics / Q000276:immunology; D000483:Alleles; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D010446:Peptide Fragments / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D000509:alpha-Fetoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D000509:alpha-Fetoproteins; D005620:Freund's Adjuvant