Prediction of high affinity class I-restricted multiple myeloma idiotype peptide epitopes

Daniel M Y Szea; Ross D Brown; Shihong Yang; John Gibson; Joy Ho; Barbara Fazekas de St Groth; Antony Basten; Douglas E Joshua

doi:10.3109/10428190309178780

Prediction of high affinity class I-restricted multiple myeloma idiotype peptide epitopes

Leuk Lymphoma. 2003 Sep;44(9):1557-68. doi: 10.3109/10428190309178780.

Authors

Daniel M Y Szea¹, Ross D Brown, Shihong Yang, John Gibson, Joy Ho, Barbara Fazekas de St Groth, Antony Basten, Douglas E Joshua

Affiliation

¹ Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia. [email protected]

PMID: 14565660
DOI: 10.3109/10428190309178780

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Aged, 80 and over
Algorithms*
Antibody Affinity
Antigen Presentation
Clone Cells / immunology
Clone Cells / pathology
Computer Systems
Female
Flow Cytometry
Histocompatibility Antigens Class I / immunology*
Humans
Immunodominant Epitopes / genetics
Immunodominant Epitopes / immunology*
Immunoglobulin Heavy Chains / genetics
Immunoglobulin Heavy Chains / immunology
Immunoglobulin Idiotypes / immunology*
Immunoglobulin Light Chains / genetics
Immunoglobulin Light Chains / immunology
Male
Middle Aged
Multiple Myeloma / immunology*
Myeloma Proteins / genetics
Myeloma Proteins / immunology*
Peptide Fragments / genetics
Peptide Fragments / immunology*
Polymerase Chain Reaction
Protein Binding
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Sequence Analysis, DNA
T-Lymphocytes, Cytotoxic / immunology*

Substances

Histocompatibility Antigens Class I
Immunodominant Epitopes
Immunoglobulin Heavy Chains
Immunoglobulin Idiotypes
Immunoglobulin Light Chains
Myeloma Proteins
Peptide Fragments
RNA, Messenger
RNA, Neoplasm