Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes

Sivasubramanian Baskar, Carol B. Kobrin, Larry W. Kwaka

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


The clonotypic surface Ig receptor expressed by malignant B cells, idiotype, is a tumor-specific antigen and an attractive target for active immunotherapy. While Ab's specific for tumor idiotype have been well described in patients with B cell malignancies, the precise antigenic epitopes in human idiotype recognized by autologous T cells remain largely unknown. We report here that T cell lines generated from lymphoma patients actively immunized with idiotype protein specifically recognized multiple, unique immunodominant epitopes in autologous tumor idiotype. Synthetic peptides corresponding to hypervariable, but not framework, regions of Ig heavy chain specifically stimulated CD4+ and CD8+ T cells to proliferate and secrete proinflammatory cytokines in an MHC-associated manner. Detailed analysis revealed a minimal determinant of an immunodominant epitope, comprising critical residues at the amino terminus that maybe a product of somatic hypermutation. Association of idiotype-specific T cell responses with previously documented molecular remissions in idiotype-vaccinated patients suggests that the newly identified T cell epitopes may be clinically relevant. Such antigenic epitopes may serve as candidates for novel peptide-vaccine strategies, and as tools to selectively expand tumor antigen-specific T cells for adoptive immunotherapy and for monitoring T cell immunity in vaccinated patients.

Original languageEnglish (US)
Pages (from-to)1498-1510
Number of pages13
JournalJournal of Clinical Investigation
Issue number10
StatePublished - May 2004
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


Dive into the research topics of 'Autologous lymphoma vaccines induce human T cell responses against multiple, unique epitopes'. Together they form a unique fingerprint.

Cite this