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Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides

Publication ,  Journal Article
Smith, MC; Pendleton, CD; Kelley, MJ; Carbone, DP; Berzofsky, JA
Published in: Journal of Investigative Medicine
January 1, 1996

Missense mutations in RAS facilitate neoplastic transformation in a variety of tissues. These mutant proteins are potential antigenic targets of tumor-specific, class I-restricted cytotoxic T lymphocyte responses. Such responses would require that peptides derived from the mutant protein bind to class I HLA molecules. RAS codons 12 and 13 lie within a sequence predicted to contain a binding motif for the most prevalent class I HLA allele, HLA-A2.1. We therefore synthesized RAS peptides (amino acids 4-20) corresponding to each of the common codon 12 missense mutations (V, D, A, C, R, S) or the wildtype (G) and a RAS peptide (amino acids 5-21) with an oncogenic codon 13 mutation, D (wildtype is G). These peptides were tested for their ability to bind to HLA-A2.1 in an MHC stabilization assay using the TAP-transporter deficient cell line, T2. The wildtype peptide along with peptides RAS12D, RAS12A, RAS12R, and RAS12S demonstrated little or no binding to HLA-A2.1. In contrast, both the RAS12C, and the RAS13D peptides stabilized HLA-A2.1 on T2 cells, indicating that they contain a segment that binds H1A-A2.1. Binding of RAS12V could not be assessed due to technical difficulties. These experimental results are consistent with the binding predictions of known motif data for these peptides. Thus, RAS12C and RAS13D peptides emerge as potential vaccine candidates for HLA.A2.1 positive individuals.

Duke Scholars

Published In

Journal of Investigative Medicine

ISSN

1708-8267

Publication Date

January 1, 1996

Volume

44

Issue

3

Related Subject Headings

  • General Clinical Medicine
  • 3202 Clinical sciences
  • 1103 Clinical Sciences
 

Citation

APA
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ICMJE
MLA
NLM
Smith, M. C., Pendleton, C. D., Kelley, M. J., Carbone, D. P., & Berzofsky, J. A. (1996). Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides. Journal of Investigative Medicine, 44(3).
Smith, M. C., C. D. Pendleton, M. J. Kelley, D. P. Carbone, and J. A. Berzofsky. “Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides.” Journal of Investigative Medicine 44, no. 3 (January 1, 1996).
Smith MC, Pendleton CD, Kelley MJ, Carbone DP, Berzofsky JA. Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides. Journal of Investigative Medicine. 1996 Jan 1;44(3).
Smith, M. C., et al. “Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides.” Journal of Investigative Medicine, vol. 44, no. 3, Jan. 1996.
Smith MC, Pendleton CD, Kelley MJ, Carbone DP, Berzofsky JA. Candidate cancer vaccines: Oncogenic mutations in ras create hla-a2.1 binding peptides. Journal of Investigative Medicine. 1996 Jan 1;44(3).

Published In

Journal of Investigative Medicine

ISSN

1708-8267

Publication Date

January 1, 1996

Volume

44

Issue

3

Related Subject Headings

  • General Clinical Medicine
  • 3202 Clinical sciences
  • 1103 Clinical Sciences