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T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA.
Eur J Immunol. 1994 Feb; 24(2):410-4.EJ

Abstract

Activated ras carry a point mutation either in codon 12, 13 or 61 which is tumor specific. Peptides derived from this oncoprotein are therefore potential tumor antigens. Essential for the feasibility of using ras-derived peptides in therapy of cancer is whether p21 ras-derived peptides can be processed, bind to human histocompatibility leukocyte antigen (HLA) and be recognized by T cells. Here we report the fine specificity and HLA restriction of several T lymphocyte clones (TLC) specific for a peptide which is derived from the second mutational hot spot in ras encoding residue 61. These TLC were generated from memory T cells present in the blood of a cancer patient and recognized a ras-derived peptide carrying Leu instead of Gln at residue 61. By sequencing of the T cell receptor (TcR) genes three sets of "sister" TLC carrying highly different TcR were identified. Two of the TLC recognized a peptide carrying the 61 Leu mutation presented by HLA-DQ8 and one recognized the same peptide presented by HLA-DQ4. By using truncated peptides derived from residues 51 to 69 of p21 ras, partially overlapping minimal epitopes could be defined. All three TLC recognized the corresponding recombinant mutant p21 ras oncoprotein carrying Leu at residue 61 presented by autologous B-lymphoblastoid cell lines (B-LCL). This demonstrates that naturally derived ras peptides from this region of p21 ras encompass the three epitopes recognized by the TLC. These results indicate that immunogenic ras-derived peptides may be used in immunotherapy of cancer where transforming ras oncoproteins are involved.

Authors+Show Affiliations

Institute of Transplantation Immunology, National Hospital, Oslo, Norway.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7507844

Citation

Gedde-Dahl, T, et al. "T Cell Epitopes Encompassing the Mutational Hot Spot Position 61 of P21 Ras. Promiscuity in Ras Peptide Binding to HLA." European Journal of Immunology, vol. 24, no. 2, 1994, pp. 410-4.
Gedde-Dahl T, Spurkland A, Fossum B, et al. T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA. Eur J Immunol. 1994;24(2):410-4.
Gedde-Dahl, T., Spurkland, A., Fossum, B., Wittinghofer, A., Thorsby, E., & Gaudernack, G. (1994). T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA. European Journal of Immunology, 24(2), 410-4.
Gedde-Dahl T, et al. T Cell Epitopes Encompassing the Mutational Hot Spot Position 61 of P21 Ras. Promiscuity in Ras Peptide Binding to HLA. Eur J Immunol. 1994;24(2):410-4. PubMed PMID: 7507844.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - T cell epitopes encompassing the mutational hot spot position 61 of p21 ras. Promiscuity in ras peptide binding to HLA. AU - Gedde-Dahl,T,3rd AU - Spurkland,A, AU - Fossum,B, AU - Wittinghofer,A, AU - Thorsby,E, AU - Gaudernack,G, PY - 1994/2/1/pubmed PY - 2001/3/28/medline PY - 1994/2/1/entrez SP - 410 EP - 4 JF - European journal of immunology JO - Eur. J. Immunol. VL - 24 IS - 2 N2 - Activated ras carry a point mutation either in codon 12, 13 or 61 which is tumor specific. Peptides derived from this oncoprotein are therefore potential tumor antigens. Essential for the feasibility of using ras-derived peptides in therapy of cancer is whether p21 ras-derived peptides can be processed, bind to human histocompatibility leukocyte antigen (HLA) and be recognized by T cells. Here we report the fine specificity and HLA restriction of several T lymphocyte clones (TLC) specific for a peptide which is derived from the second mutational hot spot in ras encoding residue 61. These TLC were generated from memory T cells present in the blood of a cancer patient and recognized a ras-derived peptide carrying Leu instead of Gln at residue 61. By sequencing of the T cell receptor (TcR) genes three sets of "sister" TLC carrying highly different TcR were identified. Two of the TLC recognized a peptide carrying the 61 Leu mutation presented by HLA-DQ8 and one recognized the same peptide presented by HLA-DQ4. By using truncated peptides derived from residues 51 to 69 of p21 ras, partially overlapping minimal epitopes could be defined. All three TLC recognized the corresponding recombinant mutant p21 ras oncoprotein carrying Leu at residue 61 presented by autologous B-lymphoblastoid cell lines (B-LCL). This demonstrates that naturally derived ras peptides from this region of p21 ras encompass the three epitopes recognized by the TLC. These results indicate that immunogenic ras-derived peptides may be used in immunotherapy of cancer where transforming ras oncoproteins are involved. SN - 0014-2980 UR - https://www.unboundmedicine.com/medline/citation/7507844/T_cell_epitopes_encompassing_the_mutational_hot_spot_position_61_of_p21_ras__Promiscuity_in_ras_peptide_binding_to_HLA_ L2 - https://doi.org/10.1002/eji.1830240221 DB - PRIME DP - Unbound Medicine ER -