Prediction of high affinity class I-restricted multiple myeloma idiotype peptide epitopes.
Idiotypic determinants are potential patient-specific tumor antigens in multiple myeloma (MM). In this study, we have determined the DNA sequence of the variable region of the tumor immunoglobulin (Ig) in 6 patients with MM. We then selected high affinity class I-restricted T-cell peptide epitopes in tumor Ig using two different internet-based epitope prediction programs. High affinity binding peptides were identified by at least one program in 4 out of 6 patients. Of these 35 peptides, only 3 scored high by both analyses. Given that all 6 patients had expanded T-cell clones with a cytotoxic (CD57+CD8+CD28-perforin+) phenotype, known to be associated with a longer survival and postulated to recognise tumor epitopes, this analysis indicates that such clones are unlikely to be exclusively directed towards tumor immuoglobulin, and suggests the need to expand the scope of the search for tumor epitopes with the ability to stimulate cytotoxic T cells in vivo.
Szea
Daniel M Y
DM
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. d.sze@centenary.usyd.edu.au
Brown
Ross D
RD
Yang
Shihong
S
Gibson
John
J
Ho
Joy
J
Fazekas de St Groth
Barbara
B
Basten
Antony
A
Joshua
Douglas E
DE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000915:Antibody Affinity; D017951:Antigen Presentation; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D003199:Computer Systems; D005260:Female; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007130:Immunoglobulin Idiotypes / Q000276:immunology*; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000276:immunology*; D009194:Myeloma Proteins / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007147:Immunoglobulin Light Chains; D009194:Myeloma Proteins; D010446:Peptide Fragments; D012333:RNA, Messenger; D012334:RNA, Neoplasm