Identification of HLA-B27-restricted cytotoxic T lymphocyte epitope from carcinoembryonic antigen.
Characterization of epitopes recognized by cytotoxic T lymphocytes (CTLs) in the sequence of tumor antigens is an important step in the development of tumor therapies. Because carcinoembryonic antigen (CEA) is a protein expressed in a high number of epithelial tumors, it is an interesting target to study. We screened for the presence of HLA-B27-restricted CTL epitopes from CEA by studying the binding to HLA-B27 of 31 synthetic peptides predicted to bind to this molecule. This afforded 16 peptides with moderate or high binding affinity. Immunization of HLA-B27 transgenic mice with the best binder peptides yielded 4 immunogenic peptides: CEA(9-17), CEA(9-18), CEA(138-146) and CEA(360-369). However, splenocytes from mice immunized with a vaccinia virus-expressing CEA recognized only CEA(9-18). These CTLs were of the CD8(+) phenotype, which upon stimulation with peptide specifically produced IFN-gamma. Moreover, they did not cross-react against peptides of region 9-18 from proteins of the CEA family. Our results show that CEA(9-18) may induce specific CTL responses against CEA.
Huarte
Eduardo
E
Departamento de Medicina Interna, Universidad de Navarra, Pamplona, Spain.
Sarobe
Pablo
P
Lasarte
Juan José
JJ
Brem
Gottfried
G
Weiss
Elisabeth H
EH
Prieto
Jesús
J
Borrás-Cuesta
Francisco
F
D000818:Animals; D001665:Binding Sites; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D003429:Cross Reactions; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus; D001613:beta 2-Microglobulin / Q000235:genetics / Q000276:immunology*
D002272:Carcinoembryonic Antigen; D018984:Epitopes, T-Lymphocyte; D015796:HLA-B27 Antigen; D010455:Peptides; D001613:beta 2-Microglobulin; D007371:Interferon-gamma