TY - JOUR
T1 - Identification of potential CTL epitopes of tumor-associated antigen MAGE-1 for five common HLA-A alleles
AU - Celis, Esteban
AU - Fikes, John
AU - Wentworth, Peggy
AU - Sidney, John
AU - Southwood, Scott
AU - Maewal, Ajesh
AU - Del Guercio, Marie France
AU - Sette, Alessandro
AU - Livingston, Brian
N1 - Funding Information:
The following HLA homozygousE BV-transformedB lymphoblastoidc ell linesw ereu seda s a sourceo f HLA molecules: Steinlin, HLA-Al (A*OlOl); GM3107, HLA-A3.2 (A*0301);B VR, HLA-All (A*1 101);K T3, HLA-A24 (A*2401); JY, HLA-A2.1 (A*0201). The EBV-transformed cell lines were obtained from the American Society for Histocompatibilitya nd Immuno-geneticsC ell Repository( Steinlina nd KT3), the Human Genetic Mutant Repository (GM3 107a nd BVR), and from Dr Linda Sherman,S cripps Clinic and Research Foundation,L a Jolla, CA (JY). The 938-mem1 elanoma celll inew asa generougs ift from Dr StevenA . Rosenberg, National CancerI nstitute,B ethesdaM, D. All cellsw ere maintainedi n tissue culture in RPMI-1640 medium (Gibco, Grand Island, NY), supplementedw ith 10% (v/v) fetal bovine serum (Gibco) at 37°C in a 5% CO,/humid air incubator.
PY - 1994/12
Y1 - 1994/12
N2 - Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ≤ 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.
AB - Identification of CTL epitopes for tumor-specific responses is important for the development of immunotherapies to treat cancer patients. We have developed a strategy to identify potential CTL epitopes based on screening of sequences of target proteins for presence of specific motifs recognized by the most common HLA-A alleles, and identification of high affinity binding peptides using in vitro quantitative assays. A systematic analysis using the sequence of the product of the tumor-associated MAGE-1 gene has been carried out. All possible peptides of nine and ten residues, containing binding motifs for HLA-A1, -A2.1, A-3.2, -A11 and -A24 were synthesized and tested for binding using a quantitative assay. Out of 237 possible peptide/MHC combinations, 47 cases demonstrated good binding affinity (Kd ≤ 500 nM). Several peptides were identified as good MHC binders for each one of the five HLA-A alleles studied (five for HLA-A1, 11 for HLA-A2.1, 10 for HLA-A3.2,16 for HLA-A11 and five for HLA-A24. Furthermore, eight of these peptides were found to bind well to more than one HLA-A allele. These results have important implications for the development of immunotherapeutic vaccines to treat malignant melanoma.
KW - MAGE-1
KW - cytotoxic T lymphocytes
KW - peptide-HLA interactions
KW - tumor antigen
UR - http://www.scopus.com/inward/record.url?scp=0028043412&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028043412&partnerID=8YFLogxK
U2 - 10.1016/0161-5890(94)90158-9
DO - 10.1016/0161-5890(94)90158-9
M3 - Article
C2 - 7823968
AN - SCOPUS:0028043412
SN - 0161-5890
VL - 31
SP - 1423
EP - 1430
JO - Molecular Immunology
JF - Molecular Immunology
IS - 18
ER -